Download PDF

Clinical Trial Results:
A Phase 2, Randomized, Double-Blind, Placebo Controlled, Dose Ranging, Dose Finding, Parallel Group Study to Assess Efficacy and Safety of PF-07081532, And Open Label Oral Semaglutide, In Adults with Type 2 Diabetes Mellitus (T2DM) Inadequately Controlled on Metformin, And Separately PF-07081532 Compared to Matching Placebo in Adults with Obesity but Without T2DM.

Summary
EudraCT number	2022-002834-15
Trial protocol	CZ HU BG
Global end of trial date	22 Sep 2023

Results information
Results version number	v1(current)
This version publication date	27 Sep 2024
First version publication date	27 Sep 2024
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

C3991004

ISRCTN number

US NCT number

NCT05579977

WHO universal trial number (UTN)

Sponsor organisation name

Pfizer Inc.

Sponsor organisation address

235 E 42nd Street, New York, United States, NY 10017

Public contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

26 Jan 2024

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

22 Sep 2023

Was the trial ended prematurely?

Yes

Main objective of the trial

To evaluate the efficacy of a range of PF-07081532 doses compared to placebo, in subjects with T2DM inadequately controlled on metformin and subjects with obesity but without T2DM.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trials subjects were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

27 Oct 2022

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 95

Country: Number of subjects enrolled

Czechia: 22

Country: Number of subjects enrolled

Hungary: 90

Country: Number of subjects enrolled

Japan: 97

Country: Number of subjects enrolled

Puerto Rico: 29

Country: Number of subjects enrolled

Bulgaria: 34

Country: Number of subjects enrolled

Poland: 89

Country: Number of subjects enrolled

United States: 445

Worldwide total number of subjects

901

EEA total number of subjects

235

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

683

From 65 to 84 years

218

85 years and over

Subject disposition

Top of page

Recruitment details

This study had 2 cohorts: Cohort 1 included subjects with type 2 diabetes mellitus (T2DM) on a background therapy of metformin. Cohort 2 included subjects with obesity But without T2DM.

Screening details

A total of 902 subjects were randomized in this study of which 1 subject did not receive treatment. The study was terminated based on pharmacokinetic data from Phase 1 drug-drug-interaction studies and laboratory measurements of elevated transaminases in these Phase 1 studies as well as this Phase 2 study.

Period 1 title

Treatment Phase

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Investigator, Subject

Are arms mutually exclusive

Yes

Placebo (T2DM)

Arm description

Subjects randomized to receive a single dose of PF-07081532-matching placebo once daily (QD) orally.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received placebo tablets orally QD.

PF-07081532 20mg (T2DM)

Arm description

Subjects randomized to receive PF-07081532 20 mg QD orally.

Arm type

Experimental

Investigational medicinal product name

PF-07081532

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-07081532 was available as tablets at unit dose strength of 20, 60 and 100 mg to be administered orally QD at the desired dose levels.

PF-07081532 40mg (T2DM)

Arm description

Subjects with T2DM inadequately controlled with metformin were administered PF-07081532 20 mg QD orally for 4 weeks followed by PF-07081532 40 mg QD orally.

Arm type

Experimental

Investigational medicinal product name

PF-07081532

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-07081532 was available as tablets at unit dose strength of 20, 60 and 100 mg to be administered orally QD at the desired dose levels.

PF-07081532 80mg (T2DM)

Arm description

Subjects with T2DM inadequately controlled with metformin were administered titrating doses of PF-07081532 20 mg QD, 40 mg QD and 60 mg QD orally for 4 weeks each followed by PF-07081532 80 mg QD orally.

Arm type

Experimental

Investigational medicinal product name

PF-07081532

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-07081532 was available as tablets at unit dose strength of 20, 60 and 100 mg to be administered orally QD at the desired dose levels.

PF-07081532 160mg (T2DM)

Arm description

Subjects with T2DM inadequately controlled with metformin were administered titrating doses of PF-07081532 20 mg QD 40 mg QD, 60 mg QD, 80 mg QD and 120 mg QD orally for 4 weeks each followed by PF-07081532 160 mg QD orally.

Arm type

Experimental

Investigational medicinal product name

PF-07081532

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-07081532 was available as tablets at unit dose strength of 20, 60 and 100 mg to be administered orally QD at the desired dose levels.

PF-07081532 260mg (T2DM)

Arm description

Subjects with T2DM inadequately controlled with metformin were administered titrating doses of PF-07081532 20 mg QD, 40 mg QD, 80 mg QD, 140 mg QD and 200 mg QD orally for 4 weeks each followed by PF-07081532 260 mg QD orally.

Arm type

Experimental

Investigational medicinal product name

PF-07081532

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-07081532 was available as tablets at unit dose strength of 20, 60 and 100 mg to be administered orally QD at the desired dose levels.

Rybelsus 14mg (T2DM)

Arm description

Subjects with T2DM inadequately controlled with metformin were administered titrating doses of Rybelsus 3 mg QD and 7 mg QD each for 4 weeks followed by 14 mg QD.

Arm type

Experimental

Investigational medicinal product name

Rybelsus

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Rybelsus was available as tablets at unit dose strength of 3, 7 and 14 mg to be administered orally QD at the desired dose levels.

Placebo (Obesity)

Arm description

Subjects randomized to receive a single dose of PF-07081532-matching placebo QD orally.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received placebo tablets orally QD.

PF-07081532 80mg (Obesity)

Arm description

Subjects with obesity were administered titrating doses of PF-07081532 20 mg QD, 40 mg QD and 60 mg QD orally for 4 weeks each followed by PF-07081532 80 mg QD orally.

Arm type

Experimental

Investigational medicinal product name

PF-07081532

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-07081532 was available as tablets at unit dose strength of 20, 60 and 100 mg to be administered orally QD at the desired dose levels.

PF-07081532 140mg (Obesity)

Arm description

Subjects with obesity were administered titrating doses of PF-07081532 20 mg QD, 40 mg QD and 60 mg QD, 80 mg QD, 120 mg QD orally for 4 weeks each followed by PF-07081532 140 mg QD orally.

Arm type

Experimental

Investigational medicinal product name

PF-07081532

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-07081532 was available as tablets at unit dose strength of 20, 60 and 100 mg to be administered orally QD at the desired dose levels.

PF-07081532 200mg (Obesity,5 steps)

Arm description

Subjects with obesity were administered titrating doses of PF-07081532 20 mg QD, 40 mg QD and 60 mg QD, 100 mg QD, 160 mg QD orally for 4 weeks each followed by PF-07081532 200 mg QD orally.

Arm type

Experimental

Investigational medicinal product name

PF-07081532

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-07081532 was available as tablets at unit dose strength of 20, 60 and 100 mg to be administered orally QD at the desired dose levels.

PF-07081532 200mg (Obesity,4 steps)

Arm description

Subjects with obesity were administered titrating doses of PF-07081532 20 mg QD, 40 mg QD and 80 mg QD, 140 mg QD orally for 4 weeks each followed by PF-07081532 200 mg QD orally.

Arm type

Experimental

Investigational medicinal product name

PF-07081532

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-07081532 was available as tablets at unit dose strength of 20, 60 and 100 mg to be administered orally QD at the desired dose levels.

PF-07081532 260mg (Obesity)

Arm description

Subjects with obesity were administered titrating doses of PF-07081532 20 mg QD, 40 mg QD and 80 mg QD, 140 mg QD, 200 mg QD orally for 4 weeks each followed by PF-07081532 260 mg QD orally.

Arm type

Experimental

Investigational medicinal product name

PF-07081532

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-07081532 was available as tablets at unit dose strength of 20, 60 and 100 mg to be administered orally QD at the desired dose levels.

Number of subjects in period 1	Placebo (T2DM)	PF-07081532 20mg (T2DM)	PF-07081532 40mg (T2DM)	PF-07081532 80mg (T2DM)	PF-07081532 160mg (T2DM)	PF-07081532 260mg (T2DM)	Rybelsus 14mg (T2DM)	Placebo (Obesity)	PF-07081532 80mg (Obesity)	PF-07081532 140mg (Obesity)	PF-07081532 200mg (Obesity,5 steps)	PF-07081532 200mg (Obesity,4 steps)	PF-07081532 260mg (Obesity)
Started	75	73	72	73	72	74	73	64	66	64	65	66	64
Completed	0	0	0	0	0	0	0	0	0	0	0	0	0
Not completed	75	73	72	73	72	74	73	64	66	64	65	66	64
Consent withdrawn by subject	2	-	-	1	2	-	1	8	3	3	5	1	3
Physician decision	-	-	-	-	-	-	-	-	-	-	-	1	-
Adverse event, non-fatal	-	3	11	10	5	17	5	5	12	20	15	24	23
Death	1	-	-	-	-	-	-	-	-	-	-	-	-
Pregnancy	-	-	-	-	-	-	-	-	-	1	-	-	-
Study terminated by sponsor	70	70	61	59	63	53	66	48	47	37	44	36	32
Unspecified	-	-	-	2	1	2	1	2	2	1	-	-	3
Lost to follow-up	-	-	-	1	1	1	-	1	2	2	1	4	3
Treatment with restricted medication needed	2	-	-	-	-	1	-	-	-	-	-	-	-

Period 2 title

Follow up Phase

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Placebo (T2DM)

Arm description

Subjects randomized to receive a single dose of PF-07081532-matching placebo once daily (QD) orally.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

PF-07081532 20mg (T2DM)

Arm description

Subjects randomized to receive PF-07081532 20 mg QD orally.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

PF-07081532 40mg (T2DM)

Arm description

Subjects randomized to receive PF-07081532 20 mg QD orally for 4 weeks, followed by 40 mg QD orally.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

PF-07081532 80mg (T2DM)

Arm description

Subjects randomized to receive PF-07081532 20 mg QD, 40 mg QD and 60 mg QD orally for 4 weeks, followed by PF-07081532 80 mg QD orally.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

PF-07081532 160mg (T2DM)

Arm description

Subjects randomized to receive PF-07081532 20 mg QD 40 mg QD, 60 mg QD, 80 mg QD and 120 mg QD orally for 4 weeks, followed by PF-07081532 160 mg QD orally.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

PF-07081532 260mg (T2DM)

Arm description

Subjects randomized to receive PF-07081532 20 mg QD, 40 mg QD, 80 mg QD, 140 mg QD and 200 mg QD orally for 4 weeks, followed by PF-07081532 260 mg QD orally.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Rybelsus 14mg (T2DM)

Arm description

Subjects randomized to receive Rybelsus 3 mg QD and 7 mg QD each for 4 weeks followed by 14 mg QD.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Placebo (Obesity)

Arm description

Subjects randomized to receive a single dose of PF-07081532-matching placebo QD orally.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

PF-07081532 80mg (Obesity)

Arm description

Subjects randomized to receive PF-07081532 20 mg QD, 40 mg QD and 60 mg QD orally for 4 weeks, followed by PF-07081532 80 mg QD orally.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

PF-07081532 140mg (Obesity)

Arm description

Subjects randomized to receive PF-07081532 20 mg QD, 40 mg QD and 60 mg QD, 80 mg QD,120 mg QD orally for 4 weeks each followed by PF-07081532 140 mg QD orally.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

PF-07081532 200mg (Obesity,5 steps)

Arm description

Subjects randomized to receive PF-07081532 20 mg QD, 40 mg QD and 60 mg QD, 100 mg QD,160 mg QD orally for 4 weeks each followed by PF-07081532 200 mg QD orally.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

PF-07081532 200mg (Obesity,4 steps)

Arm description

Subjects randomized to receive PF-07081532 20 mg QD, 40 mg QD and 80 mg QD, 140 mg QD orally for 4 weeks each followed by PF-07081532 200 mg QD orally.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

PF-07081532 260mg (Obesity)

Arm description

Subjects randomized to receive PF-07081532 20 mg QD, 40 mg QD and 80 mg QD, 140 mg QD, 200 mg QD orally for 4 weeks each followed by PF-07081532 260 mg QD orally.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Number of subjects in period 2	Placebo (T2DM)	PF-07081532 20mg (T2DM)	PF-07081532 40mg (T2DM)	PF-07081532 80mg (T2DM)	PF-07081532 160mg (T2DM)	PF-07081532 260mg (T2DM)	Rybelsus 14mg (T2DM)	Placebo (Obesity)	PF-07081532 80mg (Obesity)	PF-07081532 140mg (Obesity)	PF-07081532 200mg (Obesity,5 steps)	PF-07081532 200mg (Obesity,4 steps)	PF-07081532 260mg (Obesity)
Started	75	73	72	73	72	74	73	64	66	64	65	66	64
Completed	72	73	72	72	70	72	71	59	61	59	60	61	57
Not completed	3	0	0	1	2	2	2	5	5	5	5	5	7
Consent withdrawn by subject	2	-	-	-	1	-	1	4	2	3	3	1	3
Death	1	-	-	-	-	-	-	-	-	-	-	-	-
Lost to follow-up	-	-	-	1	1	2	1	1	3	2	2	4	4

Baseline characteristics

Top of page

Reporting group title

Placebo (T2DM)

Reporting group description

Subjects randomized to receive a single dose of PF-07081532-matching placebo once daily (QD) orally.

Reporting group title

PF-07081532 20mg (T2DM)

Reporting group description

Subjects randomized to receive PF-07081532 20 mg QD orally.

Reporting group title

PF-07081532 40mg (T2DM)

Reporting group description

Subjects with T2DM inadequately controlled with metformin were administered PF-07081532 20 mg QD orally for 4 weeks followed by PF-07081532 40 mg QD orally.

Reporting group title

PF-07081532 80mg (T2DM)

Reporting group description

Reporting group title

PF-07081532 160mg (T2DM)

Reporting group description

Reporting group title

PF-07081532 260mg (T2DM)

Reporting group description

Reporting group title

Rybelsus 14mg (T2DM)

Reporting group description

Subjects with T2DM inadequately controlled with metformin were administered titrating doses of Rybelsus 3 mg QD and 7 mg QD each for 4 weeks followed by 14 mg QD.

Reporting group title

Placebo (Obesity)

Reporting group description

Subjects randomized to receive a single dose of PF-07081532-matching placebo QD orally.

Reporting group title

PF-07081532 80mg (Obesity)

Reporting group description

Subjects with obesity were administered titrating doses of PF-07081532 20 mg QD, 40 mg QD and 60 mg QD orally for 4 weeks each followed by PF-07081532 80 mg QD orally.

Reporting group title

PF-07081532 140mg (Obesity)

Reporting group description

Subjects with obesity were administered titrating doses of PF-07081532 20 mg QD, 40 mg QD and 60 mg QD, 80 mg QD, 120 mg QD orally for 4 weeks each followed by PF-07081532 140 mg QD orally.

Reporting group title

PF-07081532 200mg (Obesity,5 steps)

Reporting group description

Subjects with obesity were administered titrating doses of PF-07081532 20 mg QD, 40 mg QD and 60 mg QD, 100 mg QD, 160 mg QD orally for 4 weeks each followed by PF-07081532 200 mg QD orally.

Reporting group title

PF-07081532 200mg (Obesity,4 steps)

Reporting group description

Subjects with obesity were administered titrating doses of PF-07081532 20 mg QD, 40 mg QD and 80 mg QD, 140 mg QD orally for 4 weeks each followed by PF-07081532 200 mg QD orally.

Reporting group title

PF-07081532 260mg (Obesity)

Reporting group description

Subjects with obesity were administered titrating doses of PF-07081532 20 mg QD, 40 mg QD and 80 mg QD, 140 mg QD, 200 mg QD orally for 4 weeks each followed by PF-07081532 260 mg QD orally.

Reporting group values	Placebo (T2DM)	PF-07081532 20mg (T2DM)	PF-07081532 40mg (T2DM)	PF-07081532 80mg (T2DM)	PF-07081532 160mg (T2DM)	PF-07081532 260mg (T2DM)	Rybelsus 14mg (T2DM)	Placebo (Obesity)	PF-07081532 80mg (Obesity)	PF-07081532 140mg (Obesity)	PF-07081532 200mg (Obesity,5 steps)	PF-07081532 200mg (Obesity,4 steps)	PF-07081532 260mg (Obesity)	Total
Number of subjects	75	73	72	73	72	74	73	64	66	64	65	66	64	901
Age Categorical
Units: Subjects
Less than (<) 18 years	0	0	0	0	0	0	0	0	0	0	0	0	0	0
18-44 years	6	8	3	4	4	6	5	17	25	24	25	21	23	171
45-64 years	40	39	52	48	44	36	43	36	33	35	34	39	33	512
More than equal to (>=) 65 years	29	26	17	21	24	32	25	11	8	5	6	6	8	218
Age continuous
Units: years
geometric mean (standard deviation)	60.0 ( 10.17 )	58.8 ( 10.17 )	58.6 ( 8.47 )	57.7 ( 9.21 )	59.6 ( 9.71 )	60.3 ( 9.76 )	59.8 ( 8.89 )	50.9 ( 13.30 )	49.3 ( 12.97 )	48.1 ( 12.44 )	47.6 ( 13.49 )	50.0 ( 10.74 )	48.5 ( 11.68 )	-
Sex: Female, Male
Units: Subjects
Female	42	30	29	31	33	31	36	36	38	45	36	42	40	469
Male	33	43	43	42	39	43	37	28	28	19	29	24	24	432
Race
Units: Subjects
American Indian or Alaska Native	1	0	0	0	0	0	0	1	1	1	0	0	1	5
Asian	12	14	17	15	13	14	11	4	3	3	3	4	6	119
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0	0	1	0	0	0	1
Black or African American	4	2	4	4	5	5	5	4	6	15	6	5	4	69
White	58	57	51	54	54	54	57	55	56	44	56	55	52	703
More than one race	0	0	0	0	0	0	0	0	0	0	0	1	1	2
Unknown or Not Reported	0	0	0	0	0	1	0	0	0	0	0	1	0	2
Ethnicity
Units: Subjects
Hispanic or Latino	14	13	8	7	14	10	8	5	8	10	14	12	10	133
Not Hispanic or Latino	61	60	63	66	58	64	64	59	58	54	51	54	54	766
Unknown or Not Reported	0	0	1	0	0	0	1	0	0	0	0	0	0	2

End points

Top of page

Reporting group title

Placebo (T2DM)

Reporting group description

Subjects randomized to receive a single dose of PF-07081532-matching placebo once daily (QD) orally.

Reporting group title

PF-07081532 20mg (T2DM)

Reporting group description

Subjects randomized to receive PF-07081532 20 mg QD orally.

Reporting group title

PF-07081532 40mg (T2DM)

Reporting group description

Subjects with T2DM inadequately controlled with metformin were administered PF-07081532 20 mg QD orally for 4 weeks followed by PF-07081532 40 mg QD orally.

Reporting group title

PF-07081532 80mg (T2DM)

Reporting group description

Reporting group title

PF-07081532 160mg (T2DM)

Reporting group description

Reporting group title

PF-07081532 260mg (T2DM)

Reporting group description

Reporting group title

Rybelsus 14mg (T2DM)

Reporting group description

Subjects with T2DM inadequately controlled with metformin were administered titrating doses of Rybelsus 3 mg QD and 7 mg QD each for 4 weeks followed by 14 mg QD.

Reporting group title

Placebo (Obesity)

Reporting group description

Subjects randomized to receive a single dose of PF-07081532-matching placebo QD orally.

Reporting group title

PF-07081532 80mg (Obesity)

Reporting group description

Subjects with obesity were administered titrating doses of PF-07081532 20 mg QD, 40 mg QD and 60 mg QD orally for 4 weeks each followed by PF-07081532 80 mg QD orally.

Reporting group title

PF-07081532 140mg (Obesity)

Reporting group description

Subjects with obesity were administered titrating doses of PF-07081532 20 mg QD, 40 mg QD and 60 mg QD, 80 mg QD, 120 mg QD orally for 4 weeks each followed by PF-07081532 140 mg QD orally.

Reporting group title

PF-07081532 200mg (Obesity,5 steps)

Reporting group description

Subjects with obesity were administered titrating doses of PF-07081532 20 mg QD, 40 mg QD and 60 mg QD, 100 mg QD, 160 mg QD orally for 4 weeks each followed by PF-07081532 200 mg QD orally.

Reporting group title

PF-07081532 200mg (Obesity,4 steps)

Reporting group description

Subjects with obesity were administered titrating doses of PF-07081532 20 mg QD, 40 mg QD and 80 mg QD, 140 mg QD orally for 4 weeks each followed by PF-07081532 200 mg QD orally.

Reporting group title

PF-07081532 260mg (Obesity)

Reporting group description

Subjects with obesity were administered titrating doses of PF-07081532 20 mg QD, 40 mg QD and 80 mg QD, 140 mg QD, 200 mg QD orally for 4 weeks each followed by PF-07081532 260 mg QD orally.

Reporting group title

Placebo (T2DM)

Reporting group description

Subjects randomized to receive a single dose of PF-07081532-matching placebo once daily (QD) orally.

Reporting group title

PF-07081532 20mg (T2DM)

Reporting group description

Subjects randomized to receive PF-07081532 20 mg QD orally.

Reporting group title

PF-07081532 40mg (T2DM)

Reporting group description

Subjects randomized to receive PF-07081532 20 mg QD orally for 4 weeks, followed by 40 mg QD orally.

Reporting group title

PF-07081532 80mg (T2DM)

Reporting group description

Subjects randomized to receive PF-07081532 20 mg QD, 40 mg QD and 60 mg QD orally for 4 weeks, followed by PF-07081532 80 mg QD orally.

Reporting group title

PF-07081532 160mg (T2DM)

Reporting group description

Subjects randomized to receive PF-07081532 20 mg QD 40 mg QD, 60 mg QD, 80 mg QD and 120 mg QD orally for 4 weeks, followed by PF-07081532 160 mg QD orally.

Reporting group title

PF-07081532 260mg (T2DM)

Reporting group description

Subjects randomized to receive PF-07081532 20 mg QD, 40 mg QD, 80 mg QD, 140 mg QD and 200 mg QD orally for 4 weeks, followed by PF-07081532 260 mg QD orally.

Reporting group title

Rybelsus 14mg (T2DM)

Reporting group description

Subjects randomized to receive Rybelsus 3 mg QD and 7 mg QD each for 4 weeks followed by 14 mg QD.

Reporting group title

Placebo (Obesity)

Reporting group description

Subjects randomized to receive a single dose of PF-07081532-matching placebo QD orally.

Reporting group title

PF-07081532 80mg (Obesity)

Reporting group description

Subjects randomized to receive PF-07081532 20 mg QD, 40 mg QD and 60 mg QD orally for 4 weeks, followed by PF-07081532 80 mg QD orally.

Reporting group title

PF-07081532 140mg (Obesity)

Reporting group description

Subjects randomized to receive PF-07081532 20 mg QD, 40 mg QD and 60 mg QD, 80 mg QD,120 mg QD orally for 4 weeks each followed by PF-07081532 140 mg QD orally.

Reporting group title

PF-07081532 200mg (Obesity,5 steps)

Reporting group description

Subjects randomized to receive PF-07081532 20 mg QD, 40 mg QD and 60 mg QD, 100 mg QD,160 mg QD orally for 4 weeks each followed by PF-07081532 200 mg QD orally.

Reporting group title

PF-07081532 200mg (Obesity,4 steps)

Reporting group description

Subjects randomized to receive PF-07081532 20 mg QD, 40 mg QD and 80 mg QD, 140 mg QD orally for 4 weeks each followed by PF-07081532 200 mg QD orally.

Reporting group title

PF-07081532 260mg (Obesity)

Reporting group description

Subjects randomized to receive PF-07081532 20 mg QD, 40 mg QD and 80 mg QD, 140 mg QD, 200 mg QD orally for 4 weeks each followed by PF-07081532 260 mg QD orally.

Subject analysis set title

Placebo (T2DM

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects with T2DM inadequately controlled with metformin were administered PF-07081532-matching placebo once daily (QD) orally.

Subject analysis set title

PF-07081532 40 mg (T2DM)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects randomized to receive PF-07081532 40 mg QD orally were included.

Subject analysis set title

PF-07081532 60mg (T2DM)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects randomized to receive PF-07081532 60 mg QD orally were included.

Subject analysis set title

PF-07081532 80 mg (T2DM)

Subject analysis set type

Safety analysis

Subject analysis set description

randomized to receive PF-07081532 80 mg QD orally were included.

Subject analysis set title

PF-07081532 120 mg (T2DM)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects randomized to receive PF-07081532 120 mg QD orally were included.

Subject analysis set title

PF-07081532 140mg (T2DM)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects randomized to receive PF-07081532 140 mg QD orally were included.

Subject analysis set title

PF-07081532 200mg (T2DM)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects randomized to receive PF-07081532 200 mg QD orally were included.

Subject analysis set title

PF-07081532 260 mg (T2DM)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects randomized to receive PF-07081532 260 mg QD orally were included.

Subject analysis set title

Rybelsus 3mg (T2DM)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects randomized to receive Rybelsus 3 mg QD orally were included.

Subject analysis set title

Rybelsus 7mg (T2DM)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects randomized to receive Rybelsus 7 mg QD orally were included.

Subject analysis set title

PF-07081532 20mg (Obesity)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects randomized to receive PF-07081532 20 mg QD orally were included.

Subject analysis set title

PF-07081532 40 mg (Obesity)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects randomized to receive PF-07081532 40 mg QD orally were included.

Subject analysis set title

PF-07081532 60 mg (Obesity)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects randomized to receive PF-07081532 60 mg QD orally were included.

Subject analysis set title

PF-07081532 100 mg (Obesity)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects randomized to receive PF-07081532 100 mg QD orally were included.

Subject analysis set title

PF-07081532 120 mg (Obesity)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects randomized to receive PF-07081532 120 mg QD orally were included.

Subject analysis set title

PF-07081532 160 mg (Obesity)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects randomized to receive PF-07081532 160 mg QD orally were included.

Subject analysis set title

PF-07081532 200 mg (Obesity)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects randomized to receive PF-07081532 200 mg QD orally were included.

Subject analysis set title

PF-07081532 260 mg (Obesity)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects randomized to receive PF-07081532 260 mg QD orally were included.

Subject analysis set title

PF-07081532 160 mg (T2DM)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects randomized to receive PF-07081532 160 mg QD orally were included.

Subject analysis set title

Rybelsus 14 mg (T2DM)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects randomized to receive Rybelsus 14 mg QD orally were included.

Subject analysis set title

PF-07081532 80 mg (Obesity)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects randomized to receive PF-07081532 80 mg QD orally were included.

Subject analysis set title

PF-07081532 140 mg (Obesity)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects randomized to receive PF-07081532 140 mg QD orally were included.

Subject analysis set title

PF-07081532 20mg (T2DM)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects randomized to receive PF-07081532 20 mg QD orally were included.

Primary: Placebo-adjusted, Change From Baseline in Percentage of Glycated Hemoglobin (HbA1c) at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)

Top of page

End point title

Placebo-adjusted, Change From Baseline in Percentage of Glycated Hemoglobin (HbA1c) at Week 32: Cohort 1 (Type 2 Diabetes Mellitus) ^[1] ^[2]

End point description

Data was not collected for this endpoint as the study was terminated prior to any subject reaching Week 32.

End point type

Primary

End point timeframe

Baseline (result closest prior to dosing on Day 1), Week 32

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical Analysis was not planned for this endpoint
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (T2DM)	PF-07081532 20mg (T2DM)	PF-07081532 40mg (T2DM)	PF-07081532 80mg (T2DM)	PF-07081532 160mg (T2DM)	PF-07081532 260mg (T2DM)	Rybelsus 14mg (T2DM)
Number of subjects analysed	0 ^[3]	0 ^[4]	0 ^[5]	0 ^[6]	0 ^[7]	0 ^[8]	0 ^[9]
Units: Percentage of HbA1c
least squares mean (standard error)	( )	( )	( )	( )	( )	( )	( )

Notes
[3] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[4] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[5] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[6] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[7] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[8] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[9] - Data was not collected for this endpoint as the study was terminated prior to Week 32.

No statistical analyses for this end point

Primary: Placebo-adjusted, Percent Change From Baseline in Body Weight at Week 32: Cohort 2 (Obesity)

Top of page

End point title

Placebo-adjusted, Percent Change From Baseline in Body Weight at Week 32: Cohort 2 (Obesity) ^[10] ^[11]

End point description

Body weight was measured using a calibrated weighing scale. Data was not collected for this endpoint as the study was terminated prior to any subject reaching Week 32.

End point type

Primary

End point timeframe

Baseline (result closest prior to dosing on Day 1), Week 32

Notes
[10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical Analysis was not planned for this endpoint
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (Obesity)	PF-07081532 80mg (Obesity)	PF-07081532 140mg (Obesity)	PF-07081532 200mg (Obesity,5 steps)	PF-07081532 200mg (Obesity,4 steps)	PF-07081532 260mg (Obesity)
Number of subjects analysed	0 ^[12]	0 ^[13]	0 ^[14]	0 ^[15]	0 ^[16]	0 ^[17]
Units: Percent change
least squares mean (standard error)	( )	( )	( )	( )	( )	( )

Notes
[12] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[13] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[14] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[15] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[16] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[17] - Data was not collected for this endpoint as the study was terminated prior to Week 32.

No statistical analyses for this end point

Secondary: Percentage of Subjects who Achieved HbA1C <7% at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)

Top of page

End point title

Percentage of Subjects who Achieved HbA1C <7% at Week 32: Cohort 1 (Type 2 Diabetes Mellitus) ^[18]

End point description

Data was not collected for this endpoint as the study was terminated prior to any subject reaching Week 32.

End point type

Secondary

End point timeframe

Baseline (result closest prior to dosing on Day 1), Week 32

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (T2DM)	PF-07081532 20mg (T2DM)	PF-07081532 40mg (T2DM)	PF-07081532 80mg (T2DM)	PF-07081532 160mg (T2DM)	PF-07081532 260mg (T2DM)	Rybelsus 14mg (T2DM)
Number of subjects analysed	0 ^[19]	0 ^[20]	0 ^[21]	0 ^[22]	0 ^[23]	0 ^[24]	0 ^[25]
Units: Percentage of subjects
number (not applicable)

Notes
[19] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[20] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[21] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[22] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[23] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[24] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[25] - Data was not collected for this endpoint as the study was terminated prior to Week 32.

No statistical analyses for this end point

Secondary: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)

Top of page

End point title

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 32: Cohort 1 (Type 2 Diabetes Mellitus) ^[26]

End point description

Data was not collected for this endpoint as the study was terminated prior to any subject reaching Week 32.

End point type

Secondary

End point timeframe

Baseline (result closest prior to dosing on Day 1), Week 32

Notes
[26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (T2DM)	PF-07081532 20mg (T2DM)	PF-07081532 40mg (T2DM)	PF-07081532 80mg (T2DM)	PF-07081532 160mg (T2DM)	PF-07081532 260mg (T2DM)	Rybelsus 14mg (T2DM)
Number of subjects analysed	0 ^[27]	0 ^[28]	0 ^[29]	0 ^[30]	0 ^[31]	0 ^[32]	0 ^[33]
Units: milligrams per deciliter (mg/dL)
arithmetic mean (standard deviation)	( )	( )	( )	( )	( )	( )	( )

Notes
[27] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[28] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[29] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[30] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[31] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[32] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[33] - Data was not collected for this endpoint as the study was terminated prior to Week 32.

No statistical analyses for this end point

Secondary: Percent Change From Baseline in Body Weight at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)

Top of page

End point title

Percent Change From Baseline in Body Weight at Week 32: Cohort 1 (Type 2 Diabetes Mellitus) ^[34]

End point description

Body weight was measured using a calibrated weighing scale. Data was not collected for Week 32 as the study was terminated prior to any subject reaching Week 32.

End point type

Secondary

End point timeframe

Baseline (result closest prior to dosing on Day 1), Week 32

Notes
[34] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (T2DM)	PF-07081532 20mg (T2DM)	PF-07081532 40mg (T2DM)	PF-07081532 80mg (T2DM)	PF-07081532 160mg (T2DM)	PF-07081532 260mg (T2DM)	Rybelsus 14mg (T2DM)
Number of subjects analysed	0 ^[35]	0 ^[36]	0 ^[37]	0 ^[38]	0 ^[39]	0 ^[40]	0 ^[41]
Units: Percent change
arithmetic mean (standard deviation)	( )	( )	( )	( )	( )	( )	( )

Notes
[35] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[36] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[37] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[38] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[39] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[40] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[41] - Data was not collected for this endpoint as the study was terminated prior to Week 32.

No statistical analyses for this end point

Secondary: Placebo-adjusted, Change From Baseline in HbA1C in the Rybelsus arm at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)

Top of page

End point title

Placebo-adjusted, Change From Baseline in HbA1C in the Rybelsus arm at Week 32: Cohort 1 (Type 2 Diabetes Mellitus) ^[42]

End point description

Data was not collected for this endpoint as the study was terminated prior to any subject reaching Week 32. This endpoint was planned to be analyzed only for rybelsus arm and placebo arm as pre-specified in the protocol.

End point type

Secondary

End point timeframe

Baseline (result closest prior to dosing on Day 1), Week 32

Notes
[42] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (T2DM)	Rybelsus 14mg (T2DM)
Number of subjects analysed	0 ^[43]	0 ^[44]
Units: Percentage of HbA1c
arithmetic mean (standard deviation)	( )	( )

Notes
[43] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[44] - Data was not collected for this endpoint as the study was terminated prior to Week 32.

No statistical analyses for this end point

Secondary: Percentage of Subjects Achieving >=5%, >=10%, and >=15% Body Weight Loss at Week 32 Relative to Baseline: Cohort 2 (Obesity)

Top of page

End point title

Percentage of Subjects Achieving >=5%, >=10%, and >=15% Body Weight Loss at Week 32 Relative to Baseline: Cohort 2 (Obesity) ^[45]

End point description

Data was not collected for this endpoint as the study was terminated prior to any subject reaching Week 32.

End point type

Secondary

End point timeframe

Baseline (result closest prior to dosing on Day 1), Week 32

Notes
[45] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (Obesity)	PF-07081532 80mg (Obesity)	PF-07081532 140mg (Obesity)	PF-07081532 200mg (Obesity,5 steps)	PF-07081532 200mg (Obesity,4 steps)	PF-07081532 260mg (Obesity)
Number of subjects analysed	0 ^[46]	0 ^[47]	0 ^[48]	0 ^[49]	0 ^[50]	0 ^[51]
Units: Percentage of subjects
number (not applicable)

Notes
[46] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[47] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[48] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[49] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[50] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[51] - Data was not collected for this endpoint as the study was terminated prior to Week 32.

No statistical analyses for this end point

Secondary: Absolute Change From Baseline in Waist Circumference at Week 32: Cohort 2 (Obesity)

Top of page

End point title

Absolute Change From Baseline in Waist Circumference at Week 32: Cohort 2 (Obesity) ^[52]

End point description

Waist circumference was measured at midpoint, between lower margin of last palpable rib and top of iliac crest (approximately 1 inch [2.54 centimeter {cm}] above the navel). It was measured by using an anthropometric tape (stretch-resistant). Data was not collected for this endpoint as the study was terminated prior to any subject reaching Week 32.

End point type

Secondary

End point timeframe

Baseline (result closest prior to dosing on Day 1), Week 32

Notes
[52] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (Obesity)	PF-07081532 80mg (Obesity)	PF-07081532 140mg (Obesity)	PF-07081532 200mg (Obesity,5 steps)	PF-07081532 200mg (Obesity,4 steps)	PF-07081532 260mg (Obesity)
Number of subjects analysed	0 ^[53]	0 ^[54]	0 ^[55]	0 ^[56]	0 ^[57]	0 ^[58]
Units: Centimeter
arithmetic mean (standard deviation)	( )	( )	( )	( )	( )	( )

Notes
[53] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[54] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[55] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[56] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[57] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[58] - Data was not collected for this endpoint as the study was terminated prior to Week 32.

No statistical analyses for this end point

Secondary: Absolute Change From Baseline in Waist-to-hip Ratio at Week 32: Cohort 2 (Obesity)

Top of page

End point title

Absolute Change From Baseline in Waist-to-hip Ratio at Week 32: Cohort 2 (Obesity) ^[59]

End point description

The hip circumference was defined as the circumference around the widest portion of the buttocks. Waist circumference was measured at midpoint, between lower margin of last palpable rib and top of iliac crest (approximately 1 inch [2.54 cm] above the navel). The measurements were performed using an anthropometric tape (stretch-resistant). Data was not collected for this endpoint as the study was terminated prior to any subject reaching Week 32.

End point type

Secondary

End point timeframe

Baseline (result closest prior to dosing on Day 1), Week 32

Notes
[59] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (Obesity)	PF-07081532 140mg (Obesity)	PF-07081532 200mg (Obesity,5 steps)	PF-07081532 200mg (Obesity,4 steps)	PF-07081532 260mg (Obesity)
Number of subjects analysed	0 ^[60]	0 ^[61]	0 ^[62]	0 ^[63]	0 ^[64]
Units: Ratio
arithmetic mean (standard deviation)	( )	( )	( )	( )	( )

Notes
[60] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[61] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[62] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[63] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[64] - Data was not collected for this endpoint as the study was terminated prior to Week 32.

No statistical analyses for this end point

Secondary: Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Week 32: Cohort 2 (Obesity)

Top of page

End point title

Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Week 32: Cohort 2 (Obesity) ^[65]

End point description

HOMA-IR was calculated as: fasting plasma insulin ([FPI]*(FPG)/405 and measured in terms of mg/dL* (milliunits per liter). Data was not collected for this endpoint as the study was terminated prior to any subject reaching Week 32.

End point type

Secondary

End point timeframe

Baseline (result closest prior to dosing on Day 1), Week 32

Notes
[65] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (Obesity)	PF-07081532 80mg (Obesity)	PF-07081532 140mg (Obesity)	PF-07081532 200mg (Obesity,5 steps)	PF-07081532 200mg (Obesity,4 steps)	PF-07081532 260mg (Obesity)
Number of subjects analysed	0 ^[66]	0 ^[67]	0 ^[68]	0 ^[69]	0 ^[70]	0 ^[71]
Units: Mg/dL* (milliunits per liter)
arithmetic mean (standard deviation)	( )	( )	( )	( )	( )	( )

Notes
[66] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[67] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[68] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[69] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[70] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[71] - Data was not collected for this endpoint as the study was terminated prior to Week 32.

No statistical analyses for this end point

Secondary: Change From Baseline in Homeostatic Model Assessment for Insulin Sensitivity (HOMA-S) at Week 32: Cohort 2 (Obesity)

Top of page

End point title

Change From Baseline in Homeostatic Model Assessment for Insulin Sensitivity (HOMA-S) at Week 32: Cohort 2 (Obesity) ^[72]

End point description

HOMA-S was calculated as (22.5/[FPI] * FPG) *100 and measured in terms of percentage sensitivity. Data was not collected for this endpoint as the study was terminated prior to any subject reaching Week 32.

End point type

Secondary

End point timeframe

Baseline (result closest prior to dosing on Day 1), Week 32

Notes
[72] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (Obesity)	PF-07081532 80mg (Obesity)	PF-07081532 140mg (Obesity)	PF-07081532 200mg (Obesity,5 steps)	PF-07081532 200mg (Obesity,4 steps)	PF-07081532 260mg (Obesity)
Number of subjects analysed	0 ^[73]	0 ^[74]	0 ^[75]	0 ^[76]	0 ^[77]	0 ^[78]
Units: Percentage sensitivity
arithmetic mean (standard deviation)	( )	( )	( )	( )	( )	( )

Notes
[73] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[74] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[75] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[76] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[77] - Data was not collected for this endpoint as the study was terminated prior to Week 32.
[78] - Data was not collected for this endpoint as the study was terminated prior to Week 32.

No statistical analyses for this end point

Secondary: Number of Subjects With Treatment Emergent Adverse Events (TEAEs): Cohort 1 (Type 2 Diabetes Mellitus)

Top of page

End point title

Number of Subjects With Treatment Emergent Adverse Events (TEAEs): Cohort 1 (Type 2 Diabetes Mellitus) ^[79]

End point description

An adverse event (AE) was any untoward medical occurrence in a subject or clinical study subject, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were any AEs that occurred on or after the first dose of treatment but before the last dose plus lag time. Safety analysis set included all subjects randomly assigned to study intervention and who took at least 1 dose of study intervention. Subjects were analyzed according to the product they actually received.

End point type

Secondary

End point timeframe

From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)

Notes
[79] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (T2DM)	PF-07081532 20mg (T2DM)	PF-07081532 40mg (T2DM)	PF-07081532 80mg (T2DM)	PF-07081532 160mg (T2DM)	PF-07081532 260mg (T2DM)	Rybelsus 14mg (T2DM)
Number of subjects analysed	75	73	72	73	72	74	73
Units: Subjects	35	37	50	44	45	56	36

No statistical analyses for this end point

Secondary: Number of Subjects With Treatment Emergent Adverse Events (TEAEs): Cohort 2 (Obesity)

Top of page

End point title

Number of Subjects With Treatment Emergent Adverse Events (TEAEs): Cohort 2 (Obesity) ^[80]

End point description

An AE was any untoward medical occurrence in a subject or clinical study subject, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were any AEs that occurred on or after the first dose of treatment but before the last dose plus lag time. Safety analysis set included all subjects randomly assigned to study intervention and who took at least 1 dose of study intervention. Subjects were analyzed according to the product they actually received.

End point type

Secondary

End point timeframe

From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)

Notes
[80] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (Obesity)	PF-07081532 80mg (Obesity)	PF-07081532 140mg (Obesity)	PF-07081532 200mg (Obesity,5 steps)	PF-07081532 200mg (Obesity,4 steps)	PF-07081532 260mg (Obesity)
Number of subjects analysed	64	66	64	65	66	64
Units: Subjects	44	54	50	56	60	53

No statistical analyses for this end point

Secondary: Number of Subjects With Serious Adverse Events (SAEs): Cohort 1 (Type 2 Diabetes Mellitus)

Top of page

End point title

Number of Subjects With Serious Adverse Events (SAEs): Cohort 1 (Type 2 Diabetes Mellitus) ^[81]

End point description

An SAE defined was any untoward medical occurrence that, at any dose, met one or more of the following criteria: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect; was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic; other important medical events. Safety analysis set included all subjects randomly assigned to study intervention and who took at least 1 dose of study intervention. Subjects were analyzed according to the product they actually received.

End point type

Secondary

End point timeframe

From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)

Notes
[81] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (T2DM)	PF-07081532 20mg (T2DM)	PF-07081532 40mg (T2DM)	PF-07081532 80mg (T2DM)	PF-07081532 160mg (T2DM)	PF-07081532 260mg (T2DM)	Rybelsus 14mg (T2DM)
Number of subjects analysed	75	73	72	73	72	74	73
Units: Subjects	1	0	3	3	1	2	1

No statistical analyses for this end point

Secondary: Number of Subjects With Serious Adverse Events (SAEs): Cohort 2 (Obesity)

Top of page

End point title

Number of Subjects With Serious Adverse Events (SAEs): Cohort 2 (Obesity) ^[82]

End point description

End point type

Secondary

End point timeframe

From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)

Notes
[82] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (Obesity)	PF-07081532 80mg (Obesity)	PF-07081532 140mg (Obesity)	PF-07081532 200mg (Obesity,5 steps)	PF-07081532 200mg (Obesity,4 steps)	PF-07081532 260mg (Obesity)
Number of subjects analysed	64	66	64	65	66	64
Units: Subjects	1	2	2	1	2	2

No statistical analyses for this end point

Secondary: Number of Subjects Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 1 (Type 2 Diabetes Mellitus)

Top of page

End point title

Number of Subjects Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 1 (Type 2 Diabetes Mellitus) ^[83]

End point description

An AE was any untoward medical occurrence in a subject or clinical study subject, temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs leading to permanent discontinuation from study were those with an AE record indicating the AE caused permanent discontinuation from the study. AEs leading to permanent discontinuation from study treatment were those AEs with an AE record indicating that action taken with study treatment was drug withdrawn but AE did not cause the subject to be discontinued from study. Safety Analysis set included all subjects randomly assigned to study intervention and who took at least 1 dose of study intervention.

End point type

Secondary

End point timeframe

From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)

Notes
[83] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (T2DM)	PF-07081532 20mg (T2DM)	PF-07081532 40mg (T2DM)	PF-07081532 80mg (T2DM)	PF-07081532 160mg (T2DM)	PF-07081532 260mg (T2DM)	Rybelsus 14mg (T2DM)
Number of subjects analysed	75	73	72	73	72	74	73
Units: Subjects
Discontinuations from study due to TEAEs	1	0	0	0	0	0	0
Discontinuations from intervention due to TEAEs	0	3	11	10	5	17	5

No statistical analyses for this end point

Secondary: Number of Subjects Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 2 (Obesity)

Top of page

End point title

Number of Subjects Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 2 (Obesity) ^[84]

End point description

An AE was any untoward medical occurrence in a subject or clinical study subject, temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs leading to permanent discontinuation from study were those with an AE record indicating the AE caused permanent discontinuation from the study. AEs leading to permanent discontinuation from study treatment were those AEs with an AE record indicating that action taken with study treatment was drug withdrawn but AE did not cause the subject to be discontinued from study. Safety Analysis set included all subjects randomly assigned to study intervention and who took at least 1 dose of study intervention.

End point type

Secondary

End point timeframe

From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)

Notes
[84] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (Obesity)	PF-07081532 80mg (Obesity)	PF-07081532 140mg (Obesity)	PF-07081532 200mg (Obesity,5 steps)	PF-07081532 200mg (Obesity,4 steps)	PF-07081532 260mg (Obesity)
Number of subjects analysed	64	66	64	65	66	64
Units: Subjects
Discontinuations from study due to TEAEs	0	0	1	0	0	1
Discontinuations from intervention due to TEAEs	5	12	19	15	24	22

No statistical analyses for this end point

Secondary: Number of Subjects With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)

Top of page

End point title

Number of Subjects With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus) ^[85]

End point description

Glucose values monitored by glucometer. Hypoglycemia =plasma/blood glucose value of <70 mg/dL (3.9 millimoles per liter [mmol/L]). Severe HAE: Subject unable to self treat due to neurological impairment (not age) and required assistance, at least one neurological symptom of memory loss, confusion, etc. Documented blood glucose<=54 mg/dL (2.7 mmol/L). Documented symptomatic: event during which symptoms of HAE were accompanied with plasma/blood glucose <70 mg/dL and prompt resolution with food intake, SC glucagon, or IV glucose. Probable symptomatic: event during which symptoms of HAE were not accompanied by a plasma glucose determination but was presumably caused by a plasma glucose <70 mg/dL. Asymptomatic: An event not accompanied by typical symptoms of HAE, plasma/blood glucose value of <70 mg/dL. Safety Analysis set used. Here, N= total number of subjects with at least one dose of the given titration dose level after pooling of data across each titration dose.

End point type

Secondary

End point timeframe

Up to week 28

Notes
[85] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	PF-07081532 160mg (T2DM)	Rybelsus 14mg (T2DM)	Placebo (T2DM	PF-07081532 40 mg (T2DM)	PF-07081532 60mg (T2DM)	PF-07081532 80 mg (T2DM)	PF-07081532 120 mg (T2DM)	PF-07081532 140mg (T2DM)	PF-07081532 200mg (T2DM)	PF-07081532 260 mg (T2DM)	Rybelsus 3mg (T2DM)	Rybelsus 7mg (T2DM)	PF-07081532 20mg (T2DM)
Number of subjects analysed	7	70	75	281	136	193	25	58	20	6	73	72	364
Units: Subjects
Severe Hypoglycemia	0	0	0	0	0	0	0	0	0	0	0	0	1
Documented Symptomatic Hypoglycemia	0	1	0	2	1	0	0	0	0	0	2	2	0
Asymptomatic Hypoglycemia	1	2	1	1	1	1	1	1	0	0	0	1	0
Probable Symptomatic Hypoglycemia	0	0	0	0	0	0	0	0	0	0	1	0	1

No statistical analyses for this end point

Secondary: Number of Subjects With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)

Top of page

End point title

Number of Subjects With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity) ^[86]

End point description

End point type

Secondary

End point timeframe

Up to week 28

Notes
[86] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (Obesity)	PF-07081532 20mg (Obesity)	PF-07081532 40 mg (Obesity)	PF-07081532 60 mg (Obesity)	PF-07081532 100 mg (Obesity)	PF-07081532 120 mg (Obesity)	PF-07081532 160 mg (Obesity)	PF-07081532 200 mg (Obesity)	PF-07081532 260 mg (Obesity)	PF-07081532 80 mg (Obesity)	PF-07081532 140 mg (Obesity)
Number of subjects analysed	64	325	310	170	56	43	47	121	28	220	140
Units: Subjects
Severe Hypoglycemia	0	0	0	0	0	0	0	0	0	0	0
Documented Symptomatic Hypoglycemia	0	0	0	0	0	0	0	0	0	0	0
Asymptomatic Hypoglycemia	0	0	0	0	0	0	0	0	0	0	0
Probable Symptomatic Hypoglycemia	0	0	0	0	0	0	0	1	0	0	0

No statistical analyses for this end point

Secondary: Number of Subjects With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)

Top of page

End point title

Number of Subjects With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus) ^[87]

End point description

Vital signs included blood pressure and pulse rate and were measured with the subjects in a seated position after at least 5 minutes of rest for the subject. Criteria for abnormalities included: Systolic Blood Pressure (millimeter of mercury [mmHg]): value more than (>) 200 and value less than (<) 90; Diastolic blood pressure: value > 100 and < 40; Pulse rate: (beats per minute [BPM]): value < 40 and > 110. Safety analysis set (SAS) included all subjects randomly assigned to study intervention and who took at least 1 dose of study intervention. Subjects were analyzed according to the product they actually received.

End point type

Secondary

End point timeframe

Up to Week 28

Notes
[87] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (T2DM)	PF-07081532 20mg (T2DM)	PF-07081532 40mg (T2DM)	PF-07081532 80mg (T2DM)	PF-07081532 160mg (T2DM)	PF-07081532 260mg (T2DM)	Rybelsus 14mg (T2DM)
Number of subjects analysed	75	73	72	73	72	74	73
Units: Subjects
Systolic Blood Pressure (mmHg) Value <90 mmHg	0	0	0	1	1	0	0
Systolic Blood Pressure (mmHg) Value >200 mmHg	0	0	0	0	0	0	0
Diastolic Blood Pressure (mmHg) Value <40 mmHg	0	0	0	0	0	0	0
Diastolic Blood Pressure (mmHg) Value >100 mmHg	0	4	2	2	2	1	2
Pulse Rate (bpm) Value <40 bpm	0	0	0	0	0	0	0
Pulse Rate (bpm) Value >110 bpm	0	1	1	0	0	1	0

No statistical analyses for this end point

Secondary: Number of Subjects With Vital Sign Abnormalities: Cohort 2 (Obesity)

Top of page

End point title

Number of Subjects With Vital Sign Abnormalities: Cohort 2 (Obesity) ^[88]

End point description

Vital signs included blood pressure and pulse rate and were measured with the subjects in a seated position after at least 5 minutes of rest for the subject. Criteria for abnormalities included: Systolic blood pressure (mmHg): value > 200 and value < 90; Diastolic blood pressure: value > 100 and < 40; Pulse rate: (BPM): value < 40 and > 110. Safety analysis set included all subjects randomly assigned to study intervention and who took at least 1 dose of study intervention. Subjects were analyzed according to the product they actually received.

End point type

Secondary

End point timeframe

Up to week 28

Notes
[88] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (Obesity)	PF-07081532 80mg (Obesity)	PF-07081532 140mg (Obesity)	PF-07081532 200mg (Obesity,5 steps)	PF-07081532 200mg (Obesity,4 steps)	PF-07081532 260mg (Obesity)
Number of subjects analysed	64	66	64	65	66	64
Units: Subjects
Systolic Blood Pressure (mmHg) Value <90 mmHg	0	3	0	2	0	1
Systolic Blood Pressure (mmHg) Value >200 mmHg	0	0	0	0	0	0
Diastolic Blood Pressure (mmHg) Value <40 mmHg	0	0	0	0	0	0
Diastolic Blood Pressure (mmHg) Value >100 mmHg	4	4	4	0	2	3
Pulse Rate (bpm) Value <40 bpm	0	0	0	0	0	0
Pulse Rate (bpm) Value >110 bpm	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Number of Subjects With Clinical Laboratory Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)

Top of page

End point title

Number of Subjects With Clinical Laboratory Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus) ^[89]

End point description

Hematology: platelets (10^9/L)< 0.5*lower limit of normal (LLN);leukocytes< 0.6*LLN and >1.5*upper limit of normal (ULN); lymphocytes and neutrophils <0.8*LLN and >1.2*ULN; basophils, eosinophils, monocytes:>1.2*ULN; prothrombin time (sec)>1.1*ULN; prothrombin international normalized ratio >1.1*ULN; clinical chemistry: bilirubin (mg/dL), indirect bilirubin:>1.5*ULN; aspartate and alanine aminotransferase, gamma glutamyl transferase (U/L):>3.0*ULN; urea nitrogen and creatinine (mg/dL)>1.3*ULN;HDL cholesterol (mg/dL)<0.8*LLN; LDL (mg/dL)>1.2*ULN, Triglycerides (mg/dL):>1.3*ULN;Potassium (milliequivalents per liter) < 0.9*LLN and >1.1*ULN;calcium (mg/dL)< 0.9*LLN,Thyroxine (nanograms/dL<0.8*LLN and >1.2*ULN, HbA1C (%)>1.3*ULN; Amylase, Lipase (U/L) and Glucose -Fasting (mg/dL)>1.5*ULN; urinalysis: pH> 8; urine glucose, ketones, protein, hemoglobin, nitrite and leukocyte esterase>=1. Number of participants with abnormalities in any of the laboratory parameters is reported. SAS was used.

End point type

Secondary

End point timeframe

Up to week 28

Notes
[89] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (T2DM)	PF-07081532 20mg (T2DM)	PF-07081532 40mg (T2DM)	PF-07081532 80mg (T2DM)	PF-07081532 160mg (T2DM)	PF-07081532 260mg (T2DM)	Rybelsus 14mg (T2DM)
Number of subjects analysed	75	73	72	72	71	73	73
Units: Subjects	67	64	57	57	61	59	64

No statistical analyses for this end point

Secondary: Number of Subjects With Clinical Laboratory Abnormalities: Cohort 2 (Obesity)

Top of page

End point title

Number of Subjects With Clinical Laboratory Abnormalities: Cohort 2 (Obesity) ^[90]

End point description

Hematology: platelets (10^9/L)< 0.5* LLN; leukocytes< 0.6*LLN and >1.5* ULN; lymphocytes and neutrophils <0.8*LLN and >1.2*ULN; basophils, eosinophils, monocytes:>1.2*ULN; prothrombin time (sec)>1.1*ULN; prothrombin international normalized ratio >1.1*ULN; clinical chemistry: bilirubin (mg/dL), indirect bilirubin:>1.5*ULN; aspartate and alanine aminotransferase, gamma glutamyl transferase (U/L):>3.0*ULN; urea nitrogen and creatinine (mg/dL)>1.3*ULN;HDL cholesterol (mg/dL)<0.8*LLN; LDL (mg/dL)>1.2*ULN, Triglycerides (mg/dL):>1.3*ULN; Potassium (milliequivalents per liter) < 0.9*LLN and >1.1*ULN; calcium (mg/dL)< 0.9*LLN, Thyroxine (nanograms/dL<0.8*LLN and >1.2*ULN, HbA1C (%)>1.3*ULN; Amylase, Lipase (U/L) and Glucose -Fasting (mg/dL)>1.5*ULN; urinalysis: pH> 8; urine glucose, ketones, protein, hemoglobin, nitrite and leukocyte esterase>=1. Number of participants with abnormalities in any of the laboratory parameters is reported. SAS was used.

End point type

Secondary

End point timeframe

Up to week 28

Notes
[90] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (Obesity)	PF-07081532 80mg (Obesity)	PF-07081532 140mg (Obesity)	PF-07081532 200mg (Obesity,5 steps)	PF-07081532 200mg (Obesity,4 steps)	PF-07081532 260mg (Obesity)
Number of subjects analysed	64	63	63	63	66	64
Units: Subjects	36	31	40	40	48	36

No statistical analyses for this end point

Secondary: Number of Subjects With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)

Top of page

End point title

Number of Subjects With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus) ^[91]

End point description

Standard 12-lead ECGs were performed after the subject had rested quietly for more than 10 minutes in a supine position utilizing an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QTcF, and QRS complex. ECG abnormalities were categorized as: PR interval (msec), Value >= 300; %Chg >= 25/50%. QRS duration (msec): Value >= 140 and %Chg >= 50%. QT interval (msec): Value > 500; QTCF interval (msec): 450 < Value <= 480, 480 < Value <= 500, Value > 500; 30 <= Change (Chg) <= 60; Chg > 60. Safety analysis set included all subjects randomly assigned to study intervention and who took at least 1 dose of study intervention. Subjects were analyzed according to the product they actually received.

End point type

Secondary

End point timeframe

Up to week 28

Notes
[91] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (T2DM)	PF-07081532 20mg (T2DM)	PF-07081532 40mg (T2DM)	PF-07081532 80mg (T2DM)	PF-07081532 160mg (T2DM)	PF-07081532 260mg (T2DM)	Rybelsus 14mg (T2DM)
Number of subjects analysed	75	73	72	73	72	74	73
Units: Subjects
PR Interval, value>=300; n=75,73,71,73,71,73,72	1	0	0	1	0	0	0
PR Interval,Change>= 25/50%;n=75,73,71,73,71,73,72	0	0	0	0	0	0	0
QRS duration, Value≥140 n=75,73,72,73,72,74,73	1	0	0	1	0	0	3
QRS duration, Change >=50%; n=75,73,72,73,72,74,73	0	0	0	0	0	0	0
QT interval, value > 500; n=75,73,72,73,72,74,73	0	0	0	0	0	0	0
QTCF, 450 < Value <=480; n=75,73,72,73,72,74,73	5	7	3	5	5	2	5
QTCF, 480 <Value <=500; n=75,73,72,73,72,74,73	0	0	0	0	0	0	1
QTCF interval, Value > 500; n=75,73,72,73,72,74,73	0	0	0	0	0	0	0
QTCF, 30 <= Change <= 60; n=75,73,72,73,72,74,73	3	7	5	4	3	10	8
QTCF interval, Change > 60; n=75,73,72,73,72,74,73	0	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Number of Subjects With ECG Abnormalities: Cohort 2 (Obesity)

Top of page

End point title

Number of Subjects With ECG Abnormalities: Cohort 2 (Obesity) ^[92]

End point description

Standard 12-lead ECGs were performed after the subject had rested quietly for more than 10 minutes in a supine position utilizing an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QTcF, and QRS complex. ECG abnormalities were categorized as: PR interval msec, Value >= 300; percentage change (%) Chg >= 25/50%. QRS duration (msec): Value >= 140 and %Chg >= 50%. QT interval (msec): Value > 500; QTCF interval (msec): 450 < Value <= 480, 480 < Value <= 500, Value > 500; 30 <= change (Chg) <= 60; Chg > 60. Safety analysis set included all subjects randomly assigned to study intervention and who took at least 1 dose of study intervention. Subjects were analyzed according to the product they actually received.

End point type

Secondary

End point timeframe

Up to week 28

Notes
[92] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (Obesity)	PF-07081532 80mg (Obesity)	PF-07081532 140mg (Obesity)	PF-07081532 200mg (Obesity,5 steps)	PF-07081532 200mg (Obesity,4 steps)	PF-07081532 260mg (Obesity)
Number of subjects analysed	64	66	64	65	66	64
Units: Subjects
PR Interval, (MSEC) value >=300	0	0	0	0	1	0
PR Interval, (MSEC) % Change >= 25/50%	0	0	0	0	1	0
QRS duration, (MSEC) value >=140	1	0	0	0	0	0
QRS duration, (MSEC) % Change >=50%	0	0	0	0	0	0
QT interval, single beat (MSEC) value > 500	0	0	0	1	0	0
QTCF interval, single beat (MSEC) 450 <Value <=480	9	3	4	2	4	7
QTCF interval, single beat (MSEC) 480 <Value <=500	0	0	0	0	0	0
QTCF interval, single beat (MSEC) Value > 500	0	0	0	0	0	0
QTCF interval, single beat (MSEC) 30 <=Change<= 60	3	8	4	4	4	3
QTCF interval, single beat (MSEC) Change > 60	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Number of Subjects According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only

Top of page

End point title

Number of Subjects According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only ^[93]

End point description

C-SSRS is an interview-based rating scale to assess suicidal ideation and behavior and had a binary response (yes/no). C-SSRS data was mapped to C-CASA per Guidance: Suicidal Ideation and Behavior: prospective assessment of occurrence in clinical trials. A subject was said to have suicidal behavior in case of any events:1) completed suicide; 2) suicide attempt 3) preparatory acts toward imminent suicidal behavior. A subject showed suicidal ideation if they responded ‘yes’ to any of the 5 questions, Wish to be dead; non-specific active suicidal thoughts active suicidal ideation with any methods (Not Plan) without Intent to Act; active suicidal ideation with some intent to act, without specific plan; Active suicidal ideation with specific plan and intent. Subjects was said to exhibit Self-injurious behavior, no suicidal intent if they responded as Yes to Has subject engaged in Non-suicidal Self-Injurious Behavior. SAS was used. This endpoint was planned to be assessed in Cohort 2 only.

End point type

Secondary

End point timeframe

Baseline (result closest prior to dosing on Day 1), anytime post-baseline (Up to Week 28)

Notes
[93] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (Obesity)	PF-07081532 80mg (Obesity)	PF-07081532 140mg (Obesity)	PF-07081532 200mg (Obesity,5 steps)	PF-07081532 200mg (Obesity,4 steps)	PF-07081532 260mg (Obesity)
Number of subjects analysed	64	66	64	65	66	64
Units: Subjects
Baseline: <1> Completed suicide	0	0	0	0	0	0
Baseline: <2> Suicide attempt	0	0	0	0	0	0
Baseline: <3> imminent suicidal behavior	0	0	0	0	0	0
Baseline: <4> Suicidal ideation	0	0	0	0	0	1
Baseline: <7> no suicidal intent	0	0	0	0	0	0
Post-Baseline: <1> Completed suicide	0	0	0	0	0	0
Post-Baseline: <2> Suicide attempt	0	0	0	0	0	0
Post-Baseline: < 3 > imminent suicidal behavior	1	0	0	0	0	0
Post-Baseline: <4> Suicidal ideation	0	0	0	0	0	1
Post-Baseline: < 7 > no suicidal intent	1	0	0	0	0	0

No statistical analyses for this end point

Other pre-specified: Placebo-adjusted, Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)

Top of page

End point title

Placebo-adjusted, Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus) ^[94]

End point description

Analysis was performed using mixed model repeated measures (MMRM) model including treatment, gender strata and time as fixed effects, baseline*time interaction, time*treatment interaction, and baseline as a covariate with time fitted as a repeated effect and participant as a random effect. Evaluable set included all subjects randomly assigned to study intervention and who took at least 1 dose of study intervention. Subjects were analyzed according to randomized intervention. Here, “Number of Subjects Analyzed” refers to subjects evaluable for this endpoint.

End point type

Other pre-specified

End point timeframe

Baseline (Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1) at Week 16

Notes
[94] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (T2DM)	PF-07081532 20mg (T2DM)	PF-07081532 40mg (T2DM)	PF-07081532 80mg (T2DM)	PF-07081532 160mg (T2DM)	PF-07081532 260mg (T2DM)	Rybelsus 14mg (T2DM)
Number of subjects analysed	24	30	21	22	25	21	24
Units: Percentage of HbA1c
least squares mean (standard error)	-0.07 ( 0.109 )	-1.03 ( 0.106 )	-1.37 ( 0.112 )	-1.44 ( 0.111 )	-1.34 ( 0.110 )	-1.36 ( 0.114 )	-0.94 ( 0.109 )

Placebo (T2DM) and PF-07081532 20mg (T2DM)

Comparison groups

Placebo (T2DM) v PF-07081532 20mg (T2DM)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.95

Confidence interval

level

90%

sides

2-sided

lower limit

-1.2

upper limit

-0.7

Placebo (T2DM) and PF-07081532 40mg (T2DM)

Comparison groups

Placebo (T2DM) v PF-07081532 40mg (T2DM)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-1.3

Confidence interval

level

90%

sides

2-sided

lower limit

-1.55

upper limit

-1.04

Placebo (T2DM) and PF-07081532 260mg (T2DM)

Comparison groups

Placebo (T2DM) v PF-07081532 260mg (T2DM)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-1.29

Confidence interval

level

90%

sides

2-sided

lower limit

-1.55

upper limit

-1.03

Placebo (T2DM) and PF-07081532 160mg (T2DM)

Comparison groups

Placebo (T2DM) v PF-07081532 160mg (T2DM)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-1.26

Confidence interval

level

90%

sides

2-sided

lower limit

-1.52

upper limit

-1.01

Placebo (T2DM) and Rybelsus 14 mg (Obesity)

Comparison groups

Placebo (T2DM) v Rybelsus 14mg (T2DM)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.86

Confidence interval

level

90%

sides

2-sided

lower limit

-1.12

upper limit

-0.61

Placebo (T2DM) and PF-07081532 80mg (T2DM)

Comparison groups

Placebo (T2DM) v PF-07081532 80mg (T2DM)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-1.37

Confidence interval

level

90%

sides

2-sided

lower limit

-1.62

upper limit

-1.11

Other pre-specified: Placebo-adjusted, Percent Change From Baseline in Body Weight at Week 20: Cohort 2 (Obesity)

Top of page

End point title

Placebo-adjusted, Percent Change From Baseline in Body Weight at Week 20: Cohort 2 (Obesity) ^[95]

End point description

Body weight was measured using a calibrated weighing scale. Analysis was performed using MMRM model including treatment, gender strata and time as fixed effects, baseline*time interaction, time*treatment interaction, and baseline as a covariate with time fitted as a repeated effect and participant as a random effect. Evaluable set included all subjects randomly assigned to study intervention and who took at least 1 dose of study intervention. Subjects were analyzed according to randomized intervention. Here, “Number of Subjects Analyzed” refers to subjects evaluable for this endpoint.

End point type

Other pre-specified

End point timeframe

Baseline (Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1), at Week 20

Notes
[95] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (Obesity)	PF-07081532 80mg (Obesity)	PF-07081532 140mg (Obesity)	PF-07081532 200mg (Obesity,5 steps)	PF-07081532 200mg (Obesity,4 steps)	PF-07081532 260mg (Obesity)
Number of subjects analysed	45	44	37	38	31	28
Units: Percent change
least squares mean (standard error)	-1.84 ( 0.612 )	-4.28 ( 0.623 )	-6.21 ( 0.654 )	-7.47 ( 0.628 )	-6.88 ( 0.638 )	-7.26 ( 0.664 )

Placebo (Obesity) and PF-07081532 80mg (Obesity)

Comparison groups

Placebo (Obesity) v PF-07081532 80mg (Obesity)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0055

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-2.44

Confidence interval

level

90%

sides

2-sided

lower limit

-3.88

upper limit

-1

Placebo (Obesity) and PF-07081532 140mg (Obesity)

Comparison groups

Placebo (Obesity) v PF-07081532 140mg (Obesity)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-4.37

Confidence interval

level

90%

sides

2-sided

lower limit

-5.84

upper limit

-2.89

Placebo (Obesity), PF-07081532 200mg (5 steps)

Comparison groups

Placebo (Obesity) v PF-07081532 200mg (Obesity,5 steps)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-5.63

Confidence interval

level

90%

sides

2-sided

lower limit

-7.07

upper limit

-4.18

Placebo (Obesity) & PF-07081532 200mg (4 steps)

Comparison groups

Placebo (Obesity) v PF-07081532 200mg (Obesity,4 steps)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-5.04

Confidence interval

level

90%

sides

2-sided

lower limit

-6.5

upper limit

-3.58

Placebo (Obesity) and PF-07081532 260mg (Obesity)

Comparison groups

Placebo (Obesity) v PF-07081532 260mg (Obesity)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-5.42

Confidence interval

level

90%

sides

2-sided

lower limit

-6.91

upper limit

-3.93

Other pre-specified: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)

Top of page

End point title

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus) ^[96]

End point description

Evaluable set included all subjects randomly assigned to study intervention and who took at least 1 dose of study intervention. Subjects were analyzed according to randomized intervention. Here, “Number of Subjects Analyzed” refers to subjects evaluable for this endpoint.

End point type

Other pre-specified

End point timeframe

Baseline (Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1), at Week 16

Notes
[96] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (T2DM)	PF-07081532 20mg (T2DM)	PF-07081532 40mg (T2DM)	PF-07081532 80mg (T2DM)	PF-07081532 160mg (T2DM)	PF-07081532 260mg (T2DM)	Rybelsus 14mg (T2DM)
Number of subjects analysed	24	30	21	22	25	21	24
Units: Milligrams per deciliter
arithmetic mean (standard deviation)	160.70 ( 39.595 )	135.59 ( 31.746 )	127.00 ( 35.928 )	132.19 ( 31.541 )	127.65 ( 28.839 )	125.07 ( 46.924 )	130.06 ( 28.120 )

No statistical analyses for this end point

Other pre-specified: Percent Change From Baseline in Body Weight at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)

Top of page

End point title

Percent Change From Baseline in Body Weight at Week 16: Cohort 1 (Type 2 Diabetes Mellitus) ^[97]

End point description

Body weight was measured using a calibrated weighing scale. Evaluable set included all subjects randomly assigned to study intervention and who took at least 1 dose of study intervention. Subjects were analyzed according to randomized intervention. Here, “Number of Subjects Analyzed” refers to subjects evaluable for this endpoint.

End point type

Other pre-specified

End point timeframe

Baseline (Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1), at Week 16

Notes
[97] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (T2DM)	PF-07081532 20mg (T2DM)	PF-07081532 40mg (T2DM)	PF-07081532 80mg (T2DM)	PF-07081532 160mg (T2DM)	PF-07081532 260mg (T2DM)	Rybelsus 14mg (T2DM)
Number of subjects analysed	29	32	30	28	28	30	27
Units: Percent change
arithmetic mean (standard deviation)	93.164 ( 22.0659 )	86.251 ( 17.3464 )	91.556 ( 23.4071 )	92.979 ( 24.5045 )	85.564 ( 17.9582 )	87.658 ( 21.6950 )	91.799 ( 20.4605 )

No statistical analyses for this end point

Other pre-specified: Absolute Change From Baseline in Waist Circumference at Week 12 and 24: Cohort 2 (Obesity)

Top of page

End point title

Absolute Change From Baseline in Waist Circumference at Week 12 and 24: Cohort 2 (Obesity) ^[98]

End point description

Waist circumference was measured at midpoint, between lower margin of last palpable rib and top of iliac crest (approximately 1 inch [2.54 cm] above the navel). It was measured by using an anthropometric tape (stretch-resistant). Evaluable set included all subjects randomly assigned to study intervention and who took at least 1 dose of study intervention. Subjects were analyzed according to randomized intervention. Here, “Number of Subjects Analyzed” refers to subjects evaluable for this endpoint. N=subjects evaluable for specified timepoints.

End point type

Other pre-specified

End point timeframe

Baseline (Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1), at Week 12, 24

Notes
[98] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (Obesity)	PF-07081532 80mg (Obesity)	PF-07081532 140mg (Obesity)	PF-07081532 200mg (Obesity,5 steps)	PF-07081532 200mg (Obesity,4 steps)	PF-07081532 260mg (Obesity)
Number of subjects analysed	57	53	49	56	53	50
Units: Cm
arithmetic mean (standard deviation)
Week 12; n=57,53,49,56,53,50	-2.702 ( 4.1726 )	-2.574 ( 5.0872 )	-3.017 ( 5.9117 )	-3.559 ( 6.5122 )	-2.191 ( 5.2942 )	-1.079 ( 4.6710 )
Week 24; n=12,12,11,9,7,4	-4.233 ( 5.3953 )	-5.147 ( 4.1807 )	-6.314 ( 10.2170 )	-2.722 ( 7.6706 )	-10.297 ( 7.7652 )	-6.450 ( 4.2123 )

No statistical analyses for this end point

Other pre-specified: Placebo-adjusted, Change From Baseline in Percentage of HbA1C in the Rybelsus arm Versus Placebo arm at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)

Top of page

End point title

Placebo-adjusted, Change From Baseline in Percentage of HbA1C in the Rybelsus arm Versus Placebo arm at Week 16: Cohort 1 (Type 2 Diabetes Mellitus) ^[99]

End point description

Analysis was performed using MMRM model including treatment, gender strata and time as fixed effects, baseline*time interaction, time*treatment interaction, and baseline as a covariate with time fitted as a repeated effect and participant as a random effect. Evaluable set included all subjects randomly assigned to study intervention and who took at least 1 dose of study intervention. Subjects were analyzed according to randomized intervention. This endpoint was planned to be analyzed only for rybelsus arm and placebo arm as pre-specified in the protocol.

End point type

Other pre-specified

End point timeframe

Baseline (Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1), at Week 16

Notes
[99] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (T2DM)	Rybelsus 14mg (T2DM)
Number of subjects analysed	24	24
Units: Percentage of HbA1C
least squares mean (standard error)	-0.07 ( 0.109 )	-0.94 ( 0.109 )

Rybelsus 14 mg (T2DM) and Placebo (T2DM)

Comparison groups

Rybelsus 14mg (T2DM) v Placebo (T2DM)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS Mean Difference

Point estimate

-0.86

Confidence interval

level

90%

sides

2-sided

lower limit

-1.12

upper limit

-0.61

Other pre-specified: Absolute Change From Baseline in Waist-to-hip Ratio at Week 12 and Week 24: Cohort 2 (Obesity)

Top of page

End point title

Absolute Change From Baseline in Waist-to-hip Ratio at Week 12 and Week 24: Cohort 2 (Obesity) ^[100]

End point description

The hip circumference was defined as the circumference around the widest portion of the buttocks. Waist circumference was measured at midpoint, between lower margin of last palpable rib and top of iliac crest (approximately 1 inch [2.54 cm] above the navel). The measurements were performed using an anthropometric tape (stretch-resistant). Evaluable set included all subjects randomly assigned to study intervention and who took at least 1 dose of study intervention. Subjects were analyzed according to randomized intervention. Here, “Number of Subjects Analyzed” refers to subjects evaluable for this endpoint.

End point type

Other pre-specified

End point timeframe

Baseline (Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1), at week 12, 24

Notes
[100] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (Obesity)	PF-07081532 80mg (Obesity)	PF-07081532 140mg (Obesity)	PF-07081532 200mg (Obesity,5 steps)	PF-07081532 200mg (Obesity,4 steps)	PF-07081532 260mg (Obesity)
Number of subjects analysed	57	53	49	56	53	50
Units: Ratio
arithmetic mean (standard deviation)
Week 12	-0.013 ( 0.0374 )	-0.002 ( 0.0459 )	-0.006 ( 0.0578 )	-0.010 ( 0.0683 )	-0.002 ( 0.0423 )	0.015 ( 0.0557 )
Week 24	-0.023 ( 0.0419 )	-0.017 ( 0.0250 )	-0.032 ( 0.0588 )	0.018 ( 0.0563 )	-0.009 ( 0.0498 )	-0.037 ( 0.0574 )

No statistical analyses for this end point

Other pre-specified: Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Week 16: Cohort 2 (Obesity)

Top of page

End point title

Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Week 16: Cohort 2 (Obesity) ^[101]

End point description

HOMA-IR was calculated as: ([FPI]*(FPG)/405 in terms of Mg/dL* (milliunits per liter). Evaluable set included all subjects randomly assigned to study intervention and who took at least 1 dose of study intervention. Subjects were analyzed according to randomized intervention. Here, “Number of Subjects Analyzed” refers to subjects evaluable for this endpoint.

End point type

Other pre-specified

End point timeframe

Baseline (Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1), Week 16

Notes
[101] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (Obesity)	PF-07081532 80mg (Obesity)	PF-07081532 140mg (Obesity)	PF-07081532 200mg (Obesity,5 steps)	PF-07081532 200mg (Obesity,4 steps)	PF-07081532 260mg (Obesity)
Number of subjects analysed	53	48	42	46	42	39
Units: Mg/dL* (milliunits per liter)
arithmetic mean (standard deviation)	0.630 ( 2.1753 )	0.185 ( 2.0579 )	-0.121 ( 4.7540 )	0.984 ( 3.9090 )	-1.172 ( 2.7360 )	-0.210 ( 1.1373 )

No statistical analyses for this end point

Other pre-specified: Change From Baseline in Homeostatic Model Assessment for Insulin Sensitivity (HOMA-S) at Week 16: Cohort 2 (Obesity)

Top of page

End point title

Change From Baseline in Homeostatic Model Assessment for Insulin Sensitivity (HOMA-S) at Week 16: Cohort 2 (Obesity) ^[102]

End point description

HOMA-S was calculated as (22.5/[FPI]*FPG)) *100 and measured in terms of percentage sensitivity. Evaluable set included all subjects randomly assigned to study intervention and who took at least 1 dose of study intervention. Subjects were analyzed according to randomized intervention. Here, “Number of Subjects Analyzed” refers to subjects evaluable for this endpoint.

End point type

Other pre-specified

End point timeframe

Baseline (Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1), Week 16

Notes
[102] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Statistical Analysis was not planned for this endpoint

End point values	Placebo (Obesity)	PF-07081532 80mg (Obesity)	PF-07081532 140mg (Obesity)	PF-07081532 200mg (Obesity,5 steps)	PF-07081532 200mg (Obesity,4 steps)	PF-07081532 260mg (Obesity)
Number of subjects analysed	53	48	42	46	42	39
Units: Percentage sensitivity
arithmetic mean (standard deviation)	-2.419 ( 51.8526 )	1.594 ( 24.1848 )	7.807 ( 26.5041 )	-7.085 ( 21.6406 )	3.497 ( 68.2570 )	-2.045 ( 28.8973 )

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Part 1 and 2: From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)

Adverse event reporting additional description

Same event may appear as both non-SAE and SAE. What is presented are distinct events. An event may be categorized as serious in 1 subject and non-serious in other subject, or a subject may have experienced both SAE and non-SAE. Safety analysis set was used.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

v26.0

Reporting group title

PF-07081532 80mg (T2DM)

Reporting group description

Reporting group title

PF-07081532 40mg (T2DM)

Reporting group description

Subjects with T2DM inadequately controlled with metformin were administered PF-07081532 20 mg QD orally for 4 weeks followed by PF-07081532 40 mg QD orally.

Reporting group title

PF-07081532 20mg (T2DM)

Reporting group description

Subjects with T2DM inadequately controlled with metformin were administered PF-07081532 20 mg QD orally.

Reporting group title

Placebo (T2DM)

Reporting group description

Subjects with T2DM inadequately controlled with metformin were administered PF-07081532-matching placebo QD orally.

Reporting group title

PF-07081532 80mg (Obesity)

Reporting group description

Subjects with obesity were administered titrating doses of PF-07081532 20 mg QD, 40 mg QD and 60 mg QD orally for 4 weeks each followed by PF-07081532 80 mg QD orally.

Reporting group title

PF-07081532 140mg (Obesity)

Reporting group description

Subjects with obesity were administered titrating doses of PF-07081532 20 mg QD, 40 mg QD and 60 mg QD, 80 mg QD,120 mg QD orally for 4 weeks each followed by PF-07081532 140 mg QD orally.

Reporting group title

PF-07081532 200mg (Obesity,5 steps)

Reporting group description

Subjects with obesity were administered titrating doses of PF-07081532 20 mg QD, 40 mg QD and 60 mg QD, 100 mg QD,160 mg QD orally for 4 weeks each followed by PF-07081532 200 mg QD orally.

Reporting group title

PF-07081532 200mg (Obesity,4 steps)

Reporting group description

Subjects with obesity were administered titrating doses of PF-07081532 20 mg QD, 40 mg QD and 80 mg QD, 140 mg QD orally for 4 weeks each followed by PF-07081532 200 mg QD orally.

Reporting group title

Placebo (Obesity)

Reporting group description

Subjects with obesity were administered a single dose of PF-07081532-matching placebo QD orally.

Reporting group title

PF-07081532 260mg (Obesity)

Reporting group description

Subjects with obesity were administered titrating doses of PF-07081532 20 mg QD, 40 mg QD and 80 mg QD, 140 mg QD, 200 mg QD orally for 4 weeks each followed by PF-07081532 260 mg QD orally.

Reporting group title

PF-07081532 260mg (T2DM)

Reporting group description

Reporting group title

PF-07081532 160mg (T2DM)

Reporting group description

Reporting group title

Rybelsus 14mg (T2DM)

Reporting group description

Subjects with T2DM inadequately controlled with metformin were administered titrating doses of Rybelsus 3 mg QD and 7 mg QD each for 4 weeks followed by 14 mg QD.

PF-07081532 80mg (T2DM)

PF-07081532 40mg (T2DM)

PF-07081532 20mg (T2DM)

Placebo (T2DM)

PF-07081532 80mg (Obesity)

PF-07081532 140mg (Obesity)

PF-07081532 200mg (Obesity,5 steps)

PF-07081532 200mg (Obesity,4 steps)

Placebo (Obesity)

PF-07081532 260mg (Obesity)

PF-07081532 260mg (T2DM)

PF-07081532 160mg (T2DM)

Rybelsus 14mg (T2DM)

Total subjects affected by serious adverse events

subjects affected / exposed

3 / 73 (4.11%)

3 / 72 (4.17%)

0 / 73 (0.00%)

1 / 75 (1.33%)

2 / 66 (3.03%)

2 / 64 (3.13%)

1 / 65 (1.54%)

2 / 66 (3.03%)

1 / 64 (1.56%)

2 / 64 (3.13%)

2 / 74 (2.70%)

1 / 72 (1.39%)

1 / 73 (1.37%)

number of deaths (all causes)

number of deaths resulting from adverse events

Investigations

Alanine aminotransferase increased

subjects affected / exposed

0 / 73 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

0 / 75 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 65 (0.00%)

1 / 66 (1.52%)

0 / 64 (0.00%)

0 / 74 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood alkaline phosphatase increased

subjects affected / exposed

0 / 73 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

0 / 75 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 65 (0.00%)

1 / 66 (1.52%)

0 / 64 (0.00%)

0 / 74 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Liver function test abnormal

subjects affected / exposed

1 / 73 (1.37%)

0 / 72 (0.00%)

0 / 73 (0.00%)

0 / 75 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 65 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 74 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Liver function test increased

subjects affected / exposed

0 / 73 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

0 / 75 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 65 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

1 / 74 (1.35%)

0 / 72 (0.00%)

0 / 73 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Carcinoid tumour

subjects affected / exposed

1 / 73 (1.37%)

0 / 72 (0.00%)

0 / 73 (0.00%)

0 / 75 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 65 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 74 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Acute myocardial infarction

subjects affected / exposed

0 / 73 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

0 / 75 (0.00%)

0 / 66 (0.00%)

1 / 64 (1.56%)

0 / 65 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 74 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Atrial fibrillation

subjects affected / exposed

0 / 73 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

0 / 75 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 65 (0.00%)

0 / 66 (0.00%)

1 / 64 (1.56%)

0 / 64 (0.00%)

0 / 74 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac arrest

subjects affected / exposed

0 / 73 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

1 / 75 (1.33%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 65 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 74 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Myocardial ischaemia

subjects affected / exposed

0 / 73 (0.00%)

1 / 72 (1.39%)

0 / 73 (0.00%)

0 / 75 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 65 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 74 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ventricular extrasystoles

subjects affected / exposed

0 / 73 (0.00%)

1 / 72 (1.39%)

0 / 73 (0.00%)

0 / 75 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 65 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 74 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Ischaemic stroke

subjects affected / exposed

0 / 73 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

0 / 75 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 65 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

1 / 64 (1.56%)

0 / 74 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Syncope

subjects affected / exposed

0 / 73 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

0 / 75 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 65 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 74 (0.00%)

0 / 72 (0.00%)

1 / 73 (1.37%)

occurrences causally related to treatment / all

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Pregnancy, puerperium and perinatal conditions

Abortion spontaneous

subjects affected / exposed

0 / 73 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

0 / 75 (0.00%)

0 / 66 (0.00%)

1 / 64 (1.56%)

0 / 65 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 74 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ear and labyrinth disorders

Vertigo

subjects affected / exposed

0 / 73 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

0 / 75 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 65 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

1 / 74 (1.35%)

0 / 72 (0.00%)

0 / 73 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Small intestinal obstruction

subjects affected / exposed

1 / 73 (1.37%)

0 / 72 (0.00%)

0 / 73 (0.00%)

0 / 75 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 65 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 74 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

Hypertransaminasaemia

subjects affected / exposed

0 / 73 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

0 / 75 (0.00%)

1 / 66 (1.52%)

0 / 64 (0.00%)

0 / 65 (0.00%)

1 / 66 (1.52%)

0 / 64 (0.00%)

0 / 74 (0.00%)

1 / 72 (1.39%)

0 / 73 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cholecystitis

subjects affected / exposed

0 / 73 (0.00%)

1 / 72 (1.39%)

0 / 73 (0.00%)

0 / 75 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 65 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 74 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Allergic respiratory symptom

subjects affected / exposed

0 / 73 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

0 / 75 (0.00%)

1 / 66 (1.52%)

0 / 64 (0.00%)

0 / 65 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 74 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Epistaxis

subjects affected / exposed

0 / 73 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

0 / 75 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 65 (0.00%)

1 / 66 (1.52%)

0 / 64 (0.00%)

0 / 74 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

COVID-19 pneumonia

subjects affected / exposed

0 / 73 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

0 / 75 (0.00%)

1 / 66 (1.52%)

0 / 64 (0.00%)

0 / 65 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 74 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cellulitis

subjects affected / exposed

0 / 73 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

0 / 75 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 65 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

1 / 64 (1.56%)

0 / 74 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Sepsis

subjects affected / exposed

0 / 73 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

0 / 75 (0.00%)

1 / 66 (1.52%)

0 / 64 (0.00%)

0 / 65 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 74 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

Gout

subjects affected / exposed

0 / 73 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

0 / 75 (0.00%)

0 / 66 (0.00%)

0 / 64 (0.00%)

1 / 65 (1.54%)

0 / 66 (0.00%)

0 / 64 (0.00%)

0 / 74 (0.00%)

0 / 72 (0.00%)

0 / 73 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Frequency threshold for reporting non-serious adverse events: 2%

Non-serious adverse events	PF-07081532 80mg (T2DM)	PF-07081532 40mg (T2DM)	PF-07081532 20mg (T2DM)	Placebo (T2DM)	PF-07081532 80mg (Obesity)	PF-07081532 140mg (Obesity)	PF-07081532 200mg (Obesity,5 steps)	PF-07081532 200mg (Obesity,4 steps)	Placebo (Obesity)	PF-07081532 260mg (Obesity)	PF-07081532 260mg (T2DM)	PF-07081532 160mg (T2DM)	Rybelsus 14mg (T2DM)
Total subjects affected by non serious adverse events
subjects affected / exposed	37 / 73 (50.68%)	46 / 72 (63.89%)	31 / 73 (42.47%)	23 / 75 (30.67%)	50 / 66 (75.76%)	48 / 64 (75.00%)	55 / 65 (84.62%)	59 / 66 (89.39%)	42 / 64 (65.63%)	53 / 64 (82.81%)	51 / 74 (68.92%)	41 / 72 (56.94%)	32 / 73 (43.84%)
Vascular disorders
Hypertension
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	2 / 66 (3.03%)	0 / 64 (0.00%)	1 / 65 (1.54%)	2 / 66 (3.03%)	4 / 64 (6.25%)	1 / 64 (1.56%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	2	0	1	2	4	1	0	0	0
Flushing
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	2 / 66 (3.03%)	0 / 64 (0.00%)	0 / 64 (0.00%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0	0
Hypotension
subjects affected / exposed	0 / 73 (0.00%)	1 / 72 (1.39%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	2 / 64 (3.13%)	0 / 65 (0.00%)	2 / 66 (3.03%)	0 / 64 (0.00%)	1 / 64 (1.56%)	0 / 74 (0.00%)	2 / 72 (2.78%)	0 / 73 (0.00%)
occurrences all number	0	1	0	0	0	2	0	2	0	1	0	2	0
General disorders and administration site conditions
Fatigue
subjects affected / exposed	1 / 73 (1.37%)	4 / 72 (5.56%)	0 / 73 (0.00%)	0 / 75 (0.00%)	7 / 66 (10.61%)	5 / 64 (7.81%)	6 / 65 (9.23%)	5 / 66 (7.58%)	5 / 64 (7.81%)	5 / 64 (7.81%)	2 / 74 (2.70%)	2 / 72 (2.78%)	2 / 73 (2.74%)
occurrences all number	1	5	0	0	11	6	9	8	5	5	2	3	2
Asthenia
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	2 / 64 (3.13%)	0 / 65 (0.00%)	1 / 66 (1.52%)	0 / 64 (0.00%)	2 / 64 (3.13%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	0	2	0	1	0	2	0	0	0
Chest discomfort
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	1 / 66 (1.52%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)	2 / 64 (3.13%)	1 / 64 (1.56%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	2	1	0	0	0
Early satiety
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	2 / 64 (3.13%)	0 / 65 (0.00%)	1 / 66 (1.52%)	0 / 64 (0.00%)	2 / 64 (3.13%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	0	2	0	1	0	2	0	0	0
Pain
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	2 / 64 (3.13%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	0	0
Respiratory, thoracic and mediastinal disorders
Nasal congestion
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	1 / 66 (1.52%)	0 / 64 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)	2 / 64 (3.13%)	0 / 64 (0.00%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	1	0	1	0	2	0	0	0	0
Cough
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	2 / 73 (2.74%)	0 / 75 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 64 (0.00%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0	0	0	0	0
Oropharyngeal pain
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	1 / 65 (1.54%)	1 / 66 (1.52%)	3 / 64 (4.69%)	1 / 64 (1.56%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	3	1	0	0	0
Sinus congestion
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	1 / 66 (1.52%)	1 / 64 (1.56%)	2 / 65 (3.08%)	1 / 66 (1.52%)	1 / 64 (1.56%)	0 / 64 (0.00%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	1	1	2	1	1	0	0	0	0
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	3 / 66 (4.55%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)	2 / 64 (3.13%)	0 / 64 (0.00%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	3	0	0	0	2	0	0	0	0
Insomnia
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	1 / 66 (1.52%)	0 / 64 (0.00%)	3 / 65 (4.62%)	1 / 66 (1.52%)	0 / 64 (0.00%)	2 / 64 (3.13%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	1	0	3	3	0	2	0	0	0
Depressed mood
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	1 / 65 (1.54%)	1 / 66 (1.52%)	2 / 64 (3.13%)	0 / 64 (0.00%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	2	0	0	0	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	2 / 73 (2.74%)	1 / 72 (1.39%)	0 / 73 (0.00%)	0 / 75 (0.00%)	1 / 66 (1.52%)	2 / 64 (3.13%)	1 / 65 (1.54%)	4 / 66 (6.06%)	2 / 64 (3.13%)	1 / 64 (1.56%)	2 / 74 (2.70%)	1 / 72 (1.39%)	0 / 73 (0.00%)
occurrences all number	2	1	0	0	1	2	1	4	2	1	2	1	0
Lipase increased
subjects affected / exposed	1 / 73 (1.37%)	4 / 72 (5.56%)	3 / 73 (4.11%)	0 / 75 (0.00%)	2 / 66 (3.03%)	0 / 64 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)	0 / 64 (0.00%)	2 / 64 (3.13%)	3 / 74 (4.05%)	0 / 72 (0.00%)	3 / 73 (4.11%)
occurrences all number	1	5	3	0	2	0	0	2	0	2	3	0	3
Aspartate aminotransferase increased
subjects affected / exposed	2 / 73 (2.74%)	1 / 72 (1.39%)	0 / 73 (0.00%)	0 / 75 (0.00%)	1 / 66 (1.52%)	2 / 64 (3.13%)	0 / 65 (0.00%)	3 / 66 (4.55%)	1 / 64 (1.56%)	1 / 64 (1.56%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	2	1	0	0	1	2	0	3	1	1	0	0	0
Liver function test increased
subjects affected / exposed	2 / 73 (2.74%)	1 / 72 (1.39%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 64 (0.00%)	1 / 74 (1.35%)	1 / 72 (1.39%)	0 / 73 (0.00%)
occurrences all number	2	1	0	0	0	0	0	0	0	0	1	1	0
Hepatic enzyme increased
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 64 (0.00%)	1 / 74 (1.35%)	2 / 72 (2.78%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	2	0
Amylase increased
subjects affected / exposed	1 / 73 (1.37%)	2 / 72 (2.78%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 64 (0.00%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	1	2	0	0	0	0	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	1 / 66 (1.52%)	0 / 64 (0.00%)	0 / 65 (0.00%)	2 / 66 (3.03%)	1 / 64 (1.56%)	0 / 64 (0.00%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	1	0	0	2	1	0	0	0	0
Ligament sprain
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)	2 / 64 (3.13%)	0 / 64 (0.00%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0	0	0
Cardiac disorders
Ventricular extrasystoles
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	2 / 73 (2.74%)	0 / 75 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 64 (0.00%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	3	0	0	0	0	0	0	0	0	0	0
Palpitations
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	1 / 64 (1.56%)	0 / 65 (0.00%)	0 / 66 (0.00%)	2 / 64 (3.13%)	0 / 64 (0.00%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	2	0	0	0	0
Nervous system disorders
Dizziness
subjects affected / exposed	1 / 73 (1.37%)	1 / 72 (1.39%)	0 / 73 (0.00%)	2 / 75 (2.67%)	4 / 66 (6.06%)	2 / 64 (3.13%)	1 / 65 (1.54%)	4 / 66 (6.06%)	3 / 64 (4.69%)	4 / 64 (6.25%)	7 / 74 (9.46%)	2 / 72 (2.78%)	0 / 73 (0.00%)
occurrences all number	2	1	0	2	5	2	1	6	3	4	8	2	0
Headache
subjects affected / exposed	2 / 73 (2.74%)	5 / 72 (6.94%)	2 / 73 (2.74%)	0 / 75 (0.00%)	7 / 66 (10.61%)	4 / 64 (6.25%)	7 / 65 (10.77%)	9 / 66 (13.64%)	5 / 64 (7.81%)	5 / 64 (7.81%)	1 / 74 (1.35%)	1 / 72 (1.39%)	2 / 73 (2.74%)
occurrences all number	3	5	2	0	9	4	11	21	5	8	1	1	2
Dysgeusia
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	2 / 73 (2.74%)	0 / 75 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	2 / 64 (3.13%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0	2	0	0	0
Migraine
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	1 / 66 (1.52%)	1 / 64 (1.56%)	2 / 65 (3.08%)	1 / 66 (1.52%)	1 / 64 (1.56%)	0 / 64 (0.00%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	1	1	2	1	1	0	0	0	0
Head discomfort
subjects affected / exposed	0 / 73 (0.00%)	2 / 72 (2.78%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 64 (0.00%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	2 / 64 (3.13%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	0	0
Thrombocytopenia
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	2 / 64 (3.13%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	0	0
Gastrointestinal disorders
Abdominal distension
subjects affected / exposed	2 / 73 (2.74%)	5 / 72 (6.94%)	1 / 73 (1.37%)	0 / 75 (0.00%)	2 / 66 (3.03%)	3 / 64 (4.69%)	1 / 65 (1.54%)	3 / 66 (4.55%)	4 / 64 (6.25%)	4 / 64 (6.25%)	1 / 74 (1.35%)	2 / 72 (2.78%)	1 / 73 (1.37%)
occurrences all number	2	6	1	0	2	3	2	6	5	5	1	2	1
Abdominal pain upper
subjects affected / exposed	1 / 73 (1.37%)	5 / 72 (6.94%)	3 / 73 (4.11%)	0 / 75 (0.00%)	1 / 66 (1.52%)	4 / 64 (6.25%)	6 / 65 (9.23%)	3 / 66 (4.55%)	1 / 64 (1.56%)	3 / 64 (4.69%)	1 / 74 (1.35%)	1 / 72 (1.39%)	1 / 73 (1.37%)
occurrences all number	1	6	4	0	1	4	7	4	1	4	1	1	1
Abdominal pain
subjects affected / exposed	1 / 73 (1.37%)	5 / 72 (6.94%)	0 / 73 (0.00%)	0 / 75 (0.00%)	3 / 66 (4.55%)	6 / 64 (9.38%)	2 / 65 (3.08%)	10 / 66 (15.15%)	4 / 64 (6.25%)	4 / 64 (6.25%)	2 / 74 (2.70%)	1 / 72 (1.39%)	2 / 73 (2.74%)
occurrences all number	1	7	0	0	3	7	3	14	6	8	2	1	2
Constipation
subjects affected / exposed	3 / 73 (4.11%)	7 / 72 (9.72%)	2 / 73 (2.74%)	1 / 75 (1.33%)	14 / 66 (21.21%)	15 / 64 (23.44%)	15 / 65 (23.08%)	23 / 66 (34.85%)	5 / 64 (7.81%)	17 / 64 (26.56%)	6 / 74 (8.11%)	4 / 72 (5.56%)	4 / 73 (5.48%)
occurrences all number	3	7	2	1	15	17	20	31	5	19	6	4	4
Eructation
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	3 / 66 (4.55%)	0 / 64 (0.00%)	2 / 65 (3.08%)	4 / 66 (6.06%)	0 / 64 (0.00%)	5 / 64 (7.81%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	4	0	3	9	0	11	0	0	0
Dyspepsia
subjects affected / exposed	4 / 73 (5.48%)	2 / 72 (2.78%)	3 / 73 (4.11%)	1 / 75 (1.33%)	6 / 66 (9.09%)	4 / 64 (6.25%)	6 / 65 (9.23%)	9 / 66 (13.64%)	2 / 64 (3.13%)	4 / 64 (6.25%)	3 / 74 (4.05%)	4 / 72 (5.56%)	2 / 73 (2.74%)
occurrences all number	5	2	3	1	6	5	7	13	2	5	3	4	2
Diarrhoea
subjects affected / exposed	8 / 73 (10.96%)	9 / 72 (12.50%)	8 / 73 (10.96%)	1 / 75 (1.33%)	10 / 66 (15.15%)	10 / 64 (15.63%)	16 / 65 (24.62%)	17 / 66 (25.76%)	12 / 64 (18.75%)	17 / 64 (26.56%)	8 / 74 (10.81%)	4 / 72 (5.56%)	6 / 73 (8.22%)
occurrences all number	8	9	9	1	15	13	23	36	17	33	10	4	7
Gastrooesophageal reflux disease
subjects affected / exposed	3 / 73 (4.11%)	2 / 72 (2.78%)	0 / 73 (0.00%)	0 / 75 (0.00%)	10 / 66 (15.15%)	6 / 64 (9.38%)	5 / 65 (7.69%)	13 / 66 (19.70%)	1 / 64 (1.56%)	6 / 64 (9.38%)	3 / 74 (4.05%)	4 / 72 (5.56%)	1 / 73 (1.37%)
occurrences all number	3	2	0	0	15	7	5	13	1	7	3	4	1
Nausea
subjects affected / exposed	21 / 73 (28.77%)	17 / 72 (23.61%)	11 / 73 (15.07%)	3 / 75 (4.00%)	34 / 66 (51.52%)	30 / 64 (46.88%)	38 / 65 (58.46%)	40 / 66 (60.61%)	8 / 64 (12.50%)	32 / 64 (50.00%)	19 / 74 (25.68%)	14 / 72 (19.44%)	10 / 73 (13.70%)
occurrences all number	31	21	14	4	51	41	56	84	9	49	22	17	11
Vomiting
subjects affected / exposed	11 / 73 (15.07%)	6 / 72 (8.33%)	1 / 73 (1.37%)	1 / 75 (1.33%)	7 / 66 (10.61%)	10 / 64 (15.63%)	21 / 65 (32.31%)	19 / 66 (28.79%)	1 / 64 (1.56%)	22 / 64 (34.38%)	11 / 74 (14.86%)	6 / 72 (8.33%)	6 / 73 (8.22%)
occurrences all number	14	8	1	1	8	13	41	30	1	38	16	11	8
Flatulence
subjects affected / exposed	1 / 73 (1.37%)	1 / 72 (1.39%)	0 / 73 (0.00%)	1 / 75 (1.33%)	1 / 66 (1.52%)	1 / 64 (1.56%)	1 / 65 (1.54%)	3 / 66 (4.55%)	2 / 64 (3.13%)	4 / 64 (6.25%)	4 / 74 (5.41%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	1	1	0	1	5	1	1	3	2	10	4	0	0
Abdominal discomfort
subjects affected / exposed	1 / 73 (1.37%)	1 / 72 (1.39%)	0 / 73 (0.00%)	0 / 75 (0.00%)	3 / 66 (4.55%)	1 / 64 (1.56%)	3 / 65 (4.62%)	2 / 66 (3.03%)	0 / 64 (0.00%)	3 / 64 (4.69%)	6 / 74 (8.11%)	5 / 72 (6.94%)	1 / 73 (1.37%)
occurrences all number	1	1	0	0	3	2	3	4	0	3	7	5	1
Dry mouth
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	2 / 65 (3.08%)	1 / 66 (1.52%)	0 / 64 (0.00%)	1 / 64 (1.56%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	0	0	2	1	0	1	0	0	0
Gastritis
subjects affected / exposed	1 / 73 (1.37%)	1 / 72 (1.39%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 64 (0.00%)	3 / 74 (4.05%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0	0	3	0	0
Hepatobiliary disorders
Hepatic function abnormal
subjects affected / exposed	1 / 73 (1.37%)	3 / 72 (4.17%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 64 (0.00%)	4 / 74 (5.41%)	2 / 72 (2.78%)	0 / 73 (0.00%)
occurrences all number	1	3	0	0	0	0	0	0	0	0	4	2	0
Cholelithiasis
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	2 / 65 (3.08%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 64 (0.00%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	0	0	0	0
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	2 / 75 (2.67%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 64 (0.00%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0	0	0
Rash
subjects affected / exposed	0 / 73 (0.00%)	1 / 72 (1.39%)	0 / 73 (0.00%)	0 / 75 (0.00%)	1 / 66 (1.52%)	2 / 64 (3.13%)	0 / 65 (0.00%)	2 / 66 (3.03%)	1 / 64 (1.56%)	1 / 64 (1.56%)	1 / 74 (1.35%)	0 / 72 (0.00%)	2 / 73 (2.74%)
occurrences all number	0	1	0	0	1	3	0	3	1	1	1	0	2
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 73 (0.00%)	3 / 72 (4.17%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 64 (0.00%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	3	0	0	0	0	0	0	0	0	0	0	0
Microalbuminuria
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	2 / 73 (2.74%)	0 / 75 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 64 (0.00%)	0 / 74 (0.00%)	0 / 72 (0.00%)	1 / 73 (1.37%)
occurrences all number	0	0	2	0	0	0	0	0	0	0	0	0	1
Haematuria
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)	2 / 64 (3.13%)	0 / 64 (0.00%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0	0	0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	1 / 73 (1.37%)	1 / 72 (1.39%)	2 / 73 (2.74%)	1 / 75 (1.33%)	2 / 66 (3.03%)	1 / 64 (1.56%)	3 / 65 (4.62%)	4 / 66 (6.06%)	2 / 64 (3.13%)	3 / 64 (4.69%)	1 / 74 (1.35%)	0 / 72 (0.00%)	1 / 73 (1.37%)
occurrences all number	1	1	2	1	2	1	3	4	2	3	1	0	1
Muscle spasms
subjects affected / exposed	1 / 73 (1.37%)	0 / 72 (0.00%)	2 / 73 (2.74%)	0 / 75 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 64 (0.00%)	0 / 74 (0.00%)	0 / 72 (0.00%)	2 / 73 (2.74%)
occurrences all number	1	0	2	0	0	0	0	0	0	0	0	0	2
Musculoskeletal chest pain
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 64 (0.00%)	2 / 74 (2.70%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2	0	0
Pain in extremity
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	1 / 66 (1.52%)	1 / 64 (1.56%)	1 / 65 (1.54%)	3 / 66 (4.55%)	1 / 64 (1.56%)	0 / 64 (0.00%)	0 / 74 (0.00%)	2 / 72 (2.78%)	1 / 73 (1.37%)
occurrences all number	0	0	0	0	1	1	1	3	1	0	0	3	1
Myalgia
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	2 / 64 (3.13%)	0 / 65 (0.00%)	0 / 66 (0.00%)	1 / 64 (1.56%)	0 / 64 (0.00%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	1	0	0	0	0
Arthralgia
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	2 / 66 (3.03%)	0 / 64 (0.00%)	2 / 65 (3.08%)	3 / 66 (4.55%)	0 / 64 (0.00%)	0 / 64 (0.00%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	2	0	2	3	0	0	0	0	0
Osteoarthritis
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)	2 / 64 (3.13%)	0 / 64 (0.00%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0	0	0
Infections and infestations
COVID-19
subjects affected / exposed	1 / 73 (1.37%)	0 / 72 (0.00%)	2 / 73 (2.74%)	0 / 75 (0.00%)	3 / 66 (4.55%)	2 / 64 (3.13%)	1 / 65 (1.54%)	2 / 66 (3.03%)	5 / 64 (7.81%)	5 / 64 (7.81%)	2 / 74 (2.70%)	1 / 72 (1.39%)	0 / 73 (0.00%)
occurrences all number	1	0	2	0	4	2	1	2	5	5	2	1	0
Nasopharyngitis
subjects affected / exposed	2 / 73 (2.74%)	3 / 72 (4.17%)	0 / 73 (0.00%)	1 / 75 (1.33%)	5 / 66 (7.58%)	2 / 64 (3.13%)	4 / 65 (6.15%)	2 / 66 (3.03%)	0 / 64 (0.00%)	4 / 64 (6.25%)	2 / 74 (2.70%)	1 / 72 (1.39%)	0 / 73 (0.00%)
occurrences all number	2	3	0	1	6	2	5	2	0	5	2	1	0
Urinary tract infection
subjects affected / exposed	1 / 73 (1.37%)	4 / 72 (5.56%)	1 / 73 (1.37%)	1 / 75 (1.33%)	2 / 66 (3.03%)	2 / 64 (3.13%)	6 / 65 (9.23%)	5 / 66 (7.58%)	2 / 64 (3.13%)	3 / 64 (4.69%)	6 / 74 (8.11%)	0 / 72 (0.00%)	4 / 73 (5.48%)
occurrences all number	2	5	1	2	2	2	7	5	3	5	7	0	5
Upper respiratory tract infection
subjects affected / exposed	0 / 73 (0.00%)	1 / 72 (1.39%)	1 / 73 (1.37%)	2 / 75 (2.67%)	2 / 66 (3.03%)	1 / 64 (1.56%)	4 / 65 (6.15%)	5 / 66 (7.58%)	3 / 64 (4.69%)	0 / 64 (0.00%)	0 / 74 (0.00%)	1 / 72 (1.39%)	3 / 73 (4.11%)
occurrences all number	0	1	1	2	2	1	4	5	3	0	0	1	3
Sinusitis
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	3 / 64 (4.69%)	1 / 65 (1.54%)	2 / 66 (3.03%)	4 / 64 (6.25%)	0 / 64 (0.00%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	0	3	1	2	4	0	0	0	0
Bronchitis
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	1 / 73 (1.37%)	1 / 75 (1.33%)	4 / 66 (6.06%)	1 / 64 (1.56%)	3 / 65 (4.62%)	0 / 66 (0.00%)	1 / 64 (1.56%)	0 / 64 (0.00%)	2 / 74 (2.70%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	2	1	4	1	3	0	1	0	2	0	0
Cellulitis
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)	2 / 64 (3.13%)	0 / 64 (0.00%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0	0	0
Cystitis
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	2 / 66 (3.03%)	0 / 64 (0.00%)	0 / 64 (0.00%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0
Gastroenteritis viral
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	2 / 64 (3.13%)	0 / 65 (0.00%)	2 / 66 (3.03%)	0 / 64 (0.00%)	1 / 64 (1.56%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	0	2	0	2	0	1	0	0	0
Gastroenteritis
subjects affected / exposed	1 / 73 (1.37%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	1 / 66 (1.52%)	1 / 64 (1.56%)	3 / 65 (4.62%)	2 / 66 (3.03%)	2 / 64 (3.13%)	1 / 64 (1.56%)	0 / 74 (0.00%)	0 / 72 (0.00%)	2 / 73 (2.74%)
occurrences all number	1	0	0	0	1	1	4	2	2	2	0	0	2
Ear infection
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	1 / 65 (1.54%)	2 / 66 (3.03%)	0 / 64 (0.00%)	0 / 64 (0.00%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	0	0	1	2	0	0	0	0	0
Viral infection
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	2 / 64 (3.13%)	0 / 65 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 64 (0.00%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	0	0	0	3	0	0	0	0	0	0	0
Pharyngitis
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	1 / 73 (1.37%)	2 / 75 (2.67%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 64 (0.00%)	0 / 74 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)
occurrences all number	0	0	1	2	0	0	0	0	0	0	0	0	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	3 / 73 (4.11%)	5 / 72 (6.94%)	1 / 73 (1.37%)	1 / 75 (1.33%)	5 / 66 (7.58%)	7 / 64 (10.94%)	3 / 65 (4.62%)	8 / 66 (12.12%)	5 / 64 (7.81%)	8 / 64 (12.50%)	7 / 74 (9.46%)	4 / 72 (5.56%)	0 / 73 (0.00%)
occurrences all number	3	5	1	1	5	7	3	9	6	12	7	4	0
Hyperglycaemia
subjects affected / exposed	1 / 73 (1.37%)	1 / 72 (1.39%)	1 / 73 (1.37%)	6 / 75 (8.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 64 (0.00%)	1 / 74 (1.35%)	1 / 72 (1.39%)	3 / 73 (4.11%)
occurrences all number	1	1	1	6	0	0	0	0	0	0	1	1	4
Hypokalaemia
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 73 (0.00%)	0 / 75 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)	0 / 64 (0.00%)	0 / 64 (0.00%)	0 / 74 (0.00%)	0 / 72 (0.00%)	2 / 73 (2.74%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2

More information

Top of page

Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

1 participant in placebo (T2DM) arm with withdrawal reason as Death in treatment phase was also counted in follow-up with the reason for discontinuation as death since exact date of last dose was unknown.

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Placebo-adjusted, Change From Baseline in Percentage of Glycated Hemoglobin (HbA1c) at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)

Primary: Placebo-adjusted, Change From Baseline in Percentage of Glycated Hemoglobin (HbA1c) at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)

Primary: Placebo-adjusted, Percent Change From Baseline in Body Weight at Week 32: Cohort 2 (Obesity)

Primary: Placebo-adjusted, Percent Change From Baseline in Body Weight at Week 32: Cohort 2 (Obesity)

Secondary: Percentage of Subjects who Achieved HbA1C <7% at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)

Secondary: Percentage of Subjects who Achieved HbA1C <7% at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)

Secondary: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)

Secondary: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)

Secondary: Percent Change From Baseline in Body Weight at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)

Secondary: Percent Change From Baseline in Body Weight at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)

Secondary: Placebo-adjusted, Change From Baseline in HbA1C in the Rybelsus arm at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)

Secondary: Placebo-adjusted, Change From Baseline in HbA1C in the Rybelsus arm at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)

Secondary: Percentage of Subjects Achieving >=5%, >=10%, and >=15% Body Weight Loss at Week 32 Relative to Baseline: Cohort 2 (Obesity)

Secondary: Percentage of Subjects Achieving >=5%, >=10%, and >=15% Body Weight Loss at Week 32 Relative to Baseline: Cohort 2 (Obesity)

Secondary: Absolute Change From Baseline in Waist Circumference at Week 32: Cohort 2 (Obesity)

Secondary: Absolute Change From Baseline in Waist Circumference at Week 32: Cohort 2 (Obesity)

Secondary: Absolute Change From Baseline in Waist-to-hip Ratio at Week 32: Cohort 2 (Obesity)

Secondary: Absolute Change From Baseline in Waist-to-hip Ratio at Week 32: Cohort 2 (Obesity)

Secondary: Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Week 32: Cohort 2 (Obesity)

Secondary: Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Week 32: Cohort 2 (Obesity)

Secondary: Change From Baseline in Homeostatic Model Assessment for Insulin Sensitivity (HOMA-S) at Week 32: Cohort 2 (Obesity)

Secondary: Change From Baseline in Homeostatic Model Assessment for Insulin Sensitivity (HOMA-S) at Week 32: Cohort 2 (Obesity)

Secondary: Number of Subjects With Treatment Emergent Adverse Events (TEAEs): Cohort 1 (Type 2 Diabetes Mellitus)

Secondary: Number of Subjects With Treatment Emergent Adverse Events (TEAEs): Cohort 1 (Type 2 Diabetes Mellitus)

Secondary: Number of Subjects With Treatment Emergent Adverse Events (TEAEs): Cohort 2 (Obesity)

Secondary: Number of Subjects With Treatment Emergent Adverse Events (TEAEs): Cohort 2 (Obesity)

Secondary: Number of Subjects With Serious Adverse Events (SAEs): Cohort 1 (Type 2 Diabetes Mellitus)

Secondary: Number of Subjects With Serious Adverse Events (SAEs): Cohort 1 (Type 2 Diabetes Mellitus)

Secondary: Number of Subjects With Serious Adverse Events (SAEs): Cohort 2 (Obesity)

Secondary: Number of Subjects With Serious Adverse Events (SAEs): Cohort 2 (Obesity)

Secondary: Number of Subjects Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 1 (Type 2 Diabetes Mellitus)

Secondary: Number of Subjects Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 1 (Type 2 Diabetes Mellitus)

Secondary: Number of Subjects Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 2 (Obesity)

Secondary: Number of Subjects Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 2 (Obesity)

Secondary: Number of Subjects With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)

Secondary: Number of Subjects With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)

Secondary: Number of Subjects With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)

Secondary: Number of Subjects With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)

Secondary: Number of Subjects With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)

Secondary: Number of Subjects With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)

Secondary: Number of Subjects With Vital Sign Abnormalities: Cohort 2 (Obesity)

Secondary: Number of Subjects With Vital Sign Abnormalities: Cohort 2 (Obesity)

Secondary: Number of Subjects With Clinical Laboratory Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)

Secondary: Number of Subjects With Clinical Laboratory Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)

Secondary: Number of Subjects With Clinical Laboratory Abnormalities: Cohort 2 (Obesity)

Secondary: Number of Subjects With Clinical Laboratory Abnormalities: Cohort 2 (Obesity)

Secondary: Number of Subjects With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)

Secondary: Number of Subjects With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)

Secondary: Number of Subjects With ECG Abnormalities: Cohort 2 (Obesity)

Secondary: Number of Subjects With ECG Abnormalities: Cohort 2 (Obesity)

Secondary: Number of Subjects According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only

Secondary: Number of Subjects According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only

Other pre-specified: Placebo-adjusted, Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)

Other pre-specified: Placebo-adjusted, Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)

Other pre-specified: Placebo-adjusted, Percent Change From Baseline in Body Weight at Week 20: Cohort 2 (Obesity)

Other pre-specified: Placebo-adjusted, Percent Change From Baseline in Body Weight at Week 20: Cohort 2 (Obesity)

Other pre-specified: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)

Other pre-specified: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)

Other pre-specified: Percent Change From Baseline in Body Weight at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)

Other pre-specified: Percent Change From Baseline in Body Weight at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)

Other pre-specified: Absolute Change From Baseline in Waist Circumference at Week 12 and 24: Cohort 2 (Obesity)

Other pre-specified: Absolute Change From Baseline in Waist Circumference at Week 12 and 24: Cohort 2 (Obesity)

Other pre-specified: Placebo-adjusted, Change From Baseline in Percentage of HbA1C in the Rybelsus arm Versus Placebo arm at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)

Other pre-specified: Placebo-adjusted, Change From Baseline in Percentage of HbA1C in the Rybelsus arm Versus Placebo arm at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)

Other pre-specified: Absolute Change From Baseline in Waist-to-hip Ratio at Week 12 and Week 24: Cohort 2 (Obesity)

Other pre-specified: Absolute Change From Baseline in Waist-to-hip Ratio at Week 12 and Week 24: Cohort 2 (Obesity)

Other pre-specified: Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Week 16: Cohort 2 (Obesity)

Other pre-specified: Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Week 16: Cohort 2 (Obesity)

Other pre-specified: Change From Baseline in Homeostatic Model Assessment for Insulin Sensitivity (HOMA-S) at Week 16: Cohort 2 (Obesity)

Other pre-specified: Change From Baseline in Homeostatic Model Assessment for Insulin Sensitivity (HOMA-S) at Week 16: Cohort 2 (Obesity)

Adverse events