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Clinical Trial Results:
Albiglutide + Insulin Glargine Versus Insulin Lispro + Insulin Glargine in the Treatment of Subjects With Type 2 Diabetes Mellitus: The Switch Study

Summary
EudraCT number	2014-001821-34
Trial protocol	HU DE IT ES GB PL
Global end of trial date	24 Jul 2017

Results information
Results version number	v1(current)
This version publication date	17 Jun 2018
First version publication date	17 Jun 2018
Other versions

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

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Trial information

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Sponsor protocol code

200977

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline

Sponsor organisation address

980 Great West Road, Brentford, Middlesex, United Kingdom,

Public contact

GSK Response Center, GlaxoSmithKline, 1 8664357343,

Scientific contact

GSK Response Center, GlaxoSmithKline, 1 8664357343,

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

21 Nov 2017

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

24 Jul 2017

Was the trial ended prematurely?

Main objective of the trial

To evaluate the glycemic effectiveness of once-weekly albiglutide as replacement of prandial insulin in participants with T2DM receiving basal-bolus insulin therapy.

Protection of trial subjects

An insulin titration surveillance process was conducted on an ongoing basis to provide medical surveillance of subject's insulin titration per the titration recommended algorithm specified in the protocol with diligent medical oversight for events of hypoglycemia and glucose readings meeting specific criteria. Additionally, there was a defined email alert process in place to identify blood glucose readings reported from participant eDiary uploads which were <=50 milligrams/deciliter (mg/dL) or >=270 mg/dL. Email alerts triggered a follow-up communication with the site to ensure appropriate patient management.

Background therapy

Evidence for comparator

Actual start date of recruitment

21 Nov 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 20

Country: Number of subjects enrolled

United States: 125

Country: Number of subjects enrolled

Mexico: 166

Country: Number of subjects enrolled

Brazil: 150

Country: Number of subjects enrolled

Hungary: 69

Country: Number of subjects enrolled

Poland: 74

Country: Number of subjects enrolled

France: 11

Country: Number of subjects enrolled

Germany: 73

Country: Number of subjects enrolled

Italy: 22

Country: Number of subjects enrolled

Spain: 46

Country: Number of subjects enrolled

United Kingdom: 6

Country: Number of subjects enrolled

Korea, Republic of: 7

Country: Number of subjects enrolled

Philippines: 28

Country: Number of subjects enrolled

South Africa: 17

Worldwide total number of subjects

814

EEA total number of subjects

301

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)

601

From 65 to 84 years

213

85 years and over

Subject disposition

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Recruitment details

This study was conducted from 21-Nov-2014 to 24-Jul-2017 at 186 centers in 14 countries: Canada, United States of America, Mexico, Brazil, Hungary, Poland, France, Germany, Italy, Spain, United Kingdom, Korea, Philippines and South Africa.

Screening details

A total of 2004 participants were screened, of which 973 participants were screen failures and 160 participants were re-screened. A total of 1031 participants then entered the standardization period, of which 217 participants were standardization failures. A total of 814 participants were randomized in the study.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Albiglutide + Insulin Glargine

Arm description

During standardization period, participants transitioned from basal bolus regimen received during screening period to insulin glargine plus insulin lispro. Eligible participants received Albiglutide 30 milligrams (mg) weekly subcutaneous (SC) injection during the treatment period and insulin lispro dose was down-titrated to half that used in the standardization period. At Week 4, Albiglutide was up-titrated to 50 mg weekly SC injection and insulin lispro was stopped for the remainder of the treatment period.

Arm type

Experimental

Investigational medicinal product name

Albiglutide

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Albiglutide was intended for self-administration as a SC injection. It was provided as a fixed dose of 30 mg of albiglutide or 50 mg of albiglutide in a 0.5 milliliters (mL) injection volume, fully disposable pen injector.

Investigational medicinal product name

Insulin Glargine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Insulin glargine was provided as injection pen for SC injection.

Insulin Lispro + Insulin Glargine

Arm description

During standardization period, participants transitioned from basal bolus regimen received during screening period to insulin glargine plus insulin lispro. Eligible participants continued with the same doses as at the end of the standardization period and doses were adjusted according to protocol-defined insulin titration algorithms. Participants received Insulin Glargine along with Insulin Lispro during the treatment period.

Arm type

Experimental

Investigational medicinal product name

Insulin Glargine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Insulin glargine was provided as injection pen for SC injection.

Investigational medicinal product name

Insulin Lispro

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

Insulin lispro was provided as injection pen for SC injection.

Number of subjects in period 1	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Started	402	412
Completed	351	350
Not completed	51	62
Adverse event, serious fatal	-	1
Consent withdrawn by subject	8	12
Physician decision	5	12
Adverse event, non-fatal	14	8
Protocol defined stopping criteria	1	3
Unknown	-	1
Study terminated by sponsor	11	11
Lost to follow-up	3	3
Lack of efficacy	3	3
Protocol deviation	6	8

Baseline characteristics

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Reporting group title

Albiglutide + Insulin Glargine

Reporting group description

Reporting group title

Insulin Lispro + Insulin Glargine

Reporting group description

During standardization period, participants transitioned from basal bolus regimen received during screening period to insulin glargine plus insulin lispro. Eligible participants continued with the same doses as at the end of the standardization period and doses were adjusted according to protocol-defined insulin titration algorithms. Participants received Insulin Glargine along with Insulin Lispro during the treatment period.

Reporting group values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine	Total
Number of subjects	402	412
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	58.0 ± 9.40	58.1 ± 9.49	-
Gender categorical
Units: Subjects
Female	228	214	442
Male	174	198	372
Race/Ethnicity, Customized
Units: Subjects
American Indian or Alaska Native	43	28	71
Asian-Central/South Asian (A) Heritage (H)	5	8	13
Asian-Japanese H/East AH/South East AH	25	24	49
Black or African American	37	32	69
Native Hawaiian or Other Pacific Islander	1	3	4
White	284	312	596
Multiple-Black or African American and White	7	5	12

End points

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Reporting group title

Albiglutide + Insulin Glargine

Reporting group description

Reporting group title

Insulin Lispro + Insulin Glargine

Reporting group description

During standardization period, participants transitioned from basal bolus regimen received during screening period to insulin glargine plus insulin lispro. Eligible participants continued with the same doses as at the end of the standardization period and doses were adjusted according to protocol-defined insulin titration algorithms. Participants received Insulin Glargine along with Insulin Lispro during the treatment period.

Subject analysis set title

Albiglutide + Insulin Glargine

Subject analysis set type

Safety analysis

Subject analysis set description

During standardization period, participants transitioned from basal bolus regimen received during screening period to insulin glargine plus insulin lispro. Eligible participants received Albiglutide 30 mg weekly SC injection during the treatment period and insulin lispro dose was down-titrated to half that used in the standardization period. At Week 4, Albiglutide was up-titrated to 50 mg weekly SC injection and insulin lispro was stopped for the remainder of the treatment period.

Subject analysis set title

Insulin Lispro + Insulin Glargine

Subject analysis set type

Safety analysis

Subject analysis set description

During standardization period, participants transitioned from basal bolus regimen received during screening period to insulin glargine plus insulin lispro. Eligible participants continued with the same doses as at the end of the standardization period and doses were adjusted according to protocol-defined insulin titration algorithms. Participants received Insulin Glargine along with Insulin Lispro during the treatment period.

Primary: Change from Baseline in glycosylated hemoglobin (HbA1c) at Week 26

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End point title

Change from Baseline in glycosylated hemoglobin (HbA1c) at Week 26

End point description

HbA1c is glycosylated hemoglobin. It was measured at Baseline and at Week 26. The analysis was conducted using mixed-effect model with repeated measures (MMRM). The model included HbA1c change from Baseline as the dependent variable; treatment, region, age category, current metformin use, visit week, treatment-by-week interaction, and Baseline HbA1c-by-week interaction as fixed effects; Baseline HbA1c as a continuous covariate; and participant as a random effect. The Baseline value was the last available non-missing value prior to the first dose of the randomized treatment, thus Baseline was Day -1. Change from Baseline is defined as the post-Baseline value minus the Baseline value. Full Analysis (FA) Population comprised of all participants who were randomly assigned to treatment (who did not receive any study treatment were also included). Only those participants available at the specified time points were analyzed.

End point type

Primary

End point timeframe

Baseline (Day -1) and Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	345 ^[1]	350 ^[2]
Units: Percentage of glycosylated hemoglobin
least squares mean (standard error)
Percentage of glycosylated hemoglobin	-1.04 ± 0.041	-1.10 ± 0.040

Notes
[1] - FA Population. Only those participants available at the specified time points were analyzed.
[2] - FA Population. Only those participants available at the specified time points were analyzed.

Statistical analysis 1

Statistical analysis description

Least Square mean of albiglutide + insulin glargine from insulin lispro + insulin glargine has been presented.

Comparison groups

Insulin Lispro + Insulin Glargine v Albiglutide + Insulin Glargine

Number of subjects included in analysis

695

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[3]

P-value

< 0.0001 ^[4]

Method

t-test, 2-sided

Parameter type

Mean difference (net)

Point estimate

0.06

Confidence interval

level

95%

sides

2-sided

lower limit

-0.05

upper limit

0.17

Notes
[3] - If the upper bound of the confidence interval is less than or equal to 0.3%, non-inferiority will be concluded.
[4] - Non-inferiority p-value. P-value from testing the null hypothesis that the difference in change from baseline least squares means (albiglutide-insulin lispro) is greater than 0.30% based on one-sided t-test with 0.025 level of significance.

Secondary: Number of participants treated with once-weekly albiglutide that were able to discontinue insulin lispro at Week 4 and did not meet prespecified criteria for severe, persistent hyperglycemia through Week 26

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End point title

Number of participants treated with once-weekly albiglutide that were able to discontinue insulin lispro at Week 4 and did not meet prespecified criteria for severe, persistent hyperglycemia through Week 26 ^[5]

End point description

Participants who did not meet prespecified criteria for severe, persistent hyperglycemia through Week 26 were those participants treated with once-weekly albiglutide that were able to replace prandial insulin without lispro re-introduction through Week 26. Number of participants treated with once-weekly albiglutide that were able to discontinue insulin lispro at Week 4 and did not meet prespecified criteria for severe, persistent hyperglycemia through Week 26 have been presented.

End point type

Secondary

End point timeframe

Up to Week 26

Notes
[5] - 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: Since the endpoint is about participants treated with Albiglutide, data has been provided for the single arm containing Albiglutide.

End point values	Albiglutide + Insulin Glargine
Number of subjects analysed	402 ^[6]
Units: Participants
Participants	218

Notes
[6] - FA Population.

No statistical analyses for this end point

Secondary: Percentage of participants with severe or documented symptomatic hypoglycemia through Week 26

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End point title

Percentage of participants with severe or documented symptomatic hypoglycemia through Week 26

End point description

Severe hypoglycemia was considered as an event requiring assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions. Plasma glucose concentrations may not be available during an event, but neurological recovery following the return of plasma glucose to normal was considered sufficient evidence that the event was induced by a low plasma glucose concentration. Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia are accompanied by a measured plasma glucose concentration <=70 milligrams per deciliters (mg/dL) (<=3.9 millimoles per liters [mmol/L]).

End point type

Secondary

End point timeframe

Up to Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	402 ^[7]	412 ^[8]
Units: Percentage of participants
number (not applicable)
Percentage of participants	57.2	75.0

Notes
[7] - FA Population. Only those participants available at the specified time points were analyzed.
[8] - FA Population. Only those participants available at the specified time points were analyzed.

Statistical analysis 1

Statistical analysis description

Odds ratio (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented.

Comparison groups

Albiglutide + Insulin Glargine v Insulin Lispro + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.0001 ^[9]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

0.43

Confidence interval

level

95%

sides

2-sided

lower limit

0.31

upper limit

0.6

Notes
[9] - Analysis was performed using non-parametric Cochran-Mantel-Haenszel (CMH) test after adjusting for Baseline HbA1c category, age category, region and current use of metformin.

Secondary: Change from Baseline in body weight at Week 26

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End point title

Change from Baseline in body weight at Week 26

End point description

End point type

Secondary

End point timeframe

Baseline (Day -1) and Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	349 ^[10]	352 ^[11]
Units: Kilograms
least squares mean (standard error)
Kilograms	-1.95 ± 0.207	2.43 ± 0.205

Notes
[10] - FA Population. Only those participants available at the specified time points were analyzed.
[11] - FA Population. Only those participants available at the specified time points were analyzed.

Statistical analysis 1

Statistical analysis description

Least Square mean difference (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented.

Comparison groups

Insulin Lispro + Insulin Glargine v Albiglutide + Insulin Glargine

Number of subjects included in analysis

701

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

t-test, 2-sided

Parameter type

Mean difference (net)

Point estimate

-4.37

Confidence interval

level

95%

sides

2-sided

lower limit

-4.93

upper limit

-3.82

Secondary: Change from Baseline to Week 26 in body weight

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End point title

Change from Baseline to Week 26 in body weight

End point description

Body weight was measured to the nearest 0.1 kilogram on a standard calibrated scale. Participants dressed in light indoor clothes (no coat, jacket, etc.) without shoes and with a voided bladder. The same equipment was used wherever possible. The Baseline value was the last available non-missing value prior to the first dose of the randomized treatment, thus Baseline was Day -1. Change from Baseline is defined as the post-Baseline value minus the Baseline value. Change from Baseline to Week 26 in body weight are presented. FA Population was analyzed. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.

End point type

Secondary

End point timeframe

Baseline (Day -1) to Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	402 ^[12]	412 ^[13]
Units: Kilograms
least squares mean (standard error)
Week 4, n=368,384	-0.55 ± 0.091	0.66 ± 0.091
Week 5, n=382,393	-0.95 ± 0.102	0.85 ± 0.102
Week 10, n=379,397	-1.71 ± 0.133	1.46 ± 0.131
Week 18, n=365,372	-1.96 ± 0.177	2.06 ± 0.175
Week 26, n=349,352	-1.95 ± 0.207	2.43 ± 0.205

Notes
[12] - FA Population.
[13] - FA Population.

Statistical analysis 1

Statistical analysis description

Least Square mean difference (albiglutide + insulin glargine minus insulin lispro + insulin glargine) at Week 4 has been presented.

Comparison groups

Albiglutide + Insulin Glargine v Insulin Lispro + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-1.21

Confidence interval

level

95%

sides

2-sided

lower limit

-1.43

upper limit

-1

Statistical analysis 2

Statistical analysis description

Least Square mean difference (albiglutide + insulin glargine minus insulin lispro + insulin glargine) at Week 5 has been presented.

Comparison groups

Albiglutide + Insulin Glargine v Insulin Lispro + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-2.05

upper limit

-1.55

Statistical analysis 3

Statistical analysis description

Least Square mean difference (albiglutide + insulin glargine minus insulin lispro + insulin glargine) at Week 10 has been presented.

Comparison groups

Albiglutide + Insulin Glargine v Insulin Lispro + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-3.17

Confidence interval

level

95%

sides

2-sided

lower limit

-3.51

upper limit

-2.82

Statistical analysis 4

Statistical analysis description

Least Square mean difference (albiglutide + insulin glargine minus insulin lispro + insulin glargine) at Week 18 has been presented.

Comparison groups

Albiglutide + Insulin Glargine v Insulin Lispro + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-4.01

Confidence interval

level

95%

sides

2-sided

lower limit

-4.48

upper limit

-3.54

Statistical analysis 5

Statistical analysis description

Least Square mean difference (albiglutide + insulin glargine minus insulin lispro + insulin glargine) at Week 26 has been presented.

Comparison groups

Albiglutide + Insulin Glargine v Insulin Lispro + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.0001

Method

t-test, 2-sided

Parameter type

Mean difference (net)

Point estimate

-4.37

Confidence interval

level

95%

sides

2-sided

lower limit

-4.93

upper limit

-3.82

Secondary: Total daily insulin dose at Week 26

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End point title

Total daily insulin dose at Week 26

End point description

Insulin dose at Week 26 was defined as the prescribed insulin dose at Week 25. Based on mixed model repeated measure (MMRM) model, prescribed total daily basal insulin dose was equal to Baseline prescribed total daily basal insulin dose + treatment + Baseline HbA1c category + region + age category + current use of metformin + visit week + treatment-by-visit week interaction + Baseline prescribed total daily basal insulin dose-by-visit week interaction. Total daily insulin dose at Week 26 is presented. Only those participants available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	342 ^[14]	341 ^[15]
Units: International Units
least squares mean (standard error)
International Units	70.36 ± 2.160	131.19 ± 2.149

Notes
[14] - FA Population. Only those participants available at the specified time points were analyzed.
[15] - FA Population. Only those participants available at the specified time points were analyzed.

Statistical analysis 1

Statistical analysis description

Least square mean difference (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented.

Comparison groups

Albiglutide + Insulin Glargine v Insulin Lispro + Insulin Glargine

Number of subjects included in analysis

683

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

t-test, 2-sided

Parameter type

Mean difference (final values)

Point estimate

-60.83

Confidence interval

level

95%

sides

2-sided

lower limit

-66.57

upper limit

-55.1

Secondary: Change from Baseline to Week 26 in HbA1c

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End point title

Change from Baseline to Week 26 in HbA1c

End point description

HbA1c is glycosylated hemoglobin and was measured up to Week 26. The Baseline value was the last available non-missing value prior to the first dose of the randomized treatment, thus Baseline was Day -1. Change from Baseline is defined as the post-Baseline value minus the Baseline value. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.

End point type

Secondary

End point timeframe

Baseline to Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	402 ^[16]	412 ^[17]
Units: Percentage of glycosylated hemoglobin
least squares mean (standard error)
Week 4, n=358,375	-0.59 ± 0.023	-0.47 ± 0.023
Week 5, n=374,392	-0.67 ± 0.026	-0.58 ± 0.025
Week 10, n=376,390	-0.88 ± 0.034	-0.96 ± 0.033
Week 18, n=360,365	-1.04 ± 0.038	-1.14 ± 0.038
Week 26, n=345,350	-1.04 ± 0.041	-1.1 ± 0.040

Notes
[16] - FA Population.
[17] - FA Population.

Statistical analysis 1

Statistical analysis description

Least square mean difference (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 4.

Comparison groups

Albiglutide + Insulin Glargine v Insulin Lispro + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[18]

P-value

< 0.0001

Method

t-test, 1-sided

Parameter type

Mean difference (net)

Point estimate

-0.12

Confidence interval

level

95%

sides

2-sided

lower limit

-0.18

upper limit

-0.07

Notes
[18] - Difference in change from Baseline least squares means (albiglutide - insulin lispro) is greater than 0.30% based on one-sided t-test with 0.025 level of significance

Statistical analysis 2

Statistical analysis description

Least square mean difference (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 5.

Comparison groups

Albiglutide + Insulin Glargine v Insulin Lispro + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[19]

P-value

< 0.0001

Method

t-test, 1-sided

Parameter type

Mean difference (net)

Point estimate

-0.09

Confidence interval

level

95%

sides

2-sided

lower limit

-0.15

upper limit

-0.02

Notes
[19] - Difference in change from Baseline least squares means (albiglutide - insulin lispro) is greater than 0.30% based on one-sided t-test with 0.025 level of significance

Statistical analysis 3

Statistical analysis description

Least square mean difference (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 10.

Comparison groups

Albiglutide + Insulin Glargine v Insulin Lispro + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[20]

P-value

< 0.0001

Method

t-test, 1-sided

Parameter type

Mean difference (net)

Point estimate

0.08

Confidence interval

level

95%

sides

2-sided

lower limit

-0.01

upper limit

0.17

Notes
[20] - Difference in change from Baseline least squares means (albiglutide - insulin lispro) is greater than 0.30% based on one-sided t-test with 0.025 level of significance

Statistical analysis 4

Statistical analysis description

Least square mean difference (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 18.

Comparison groups

Albiglutide + Insulin Glargine v Insulin Lispro + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[21]

P-value

< 0.0001

Method

t-test, 1-sided

Parameter type

Mean difference (net)

Point estimate

0.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.01

upper limit

0.21

Notes
[21] - Difference in change from Baseline least squares means (albiglutide - insulin lispro) is greater than 0.30% based on one-sided t-test with 0.025 level of significance

Statistical analysis 5

Statistical analysis description

Least square mean difference (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 26.

Comparison groups

Albiglutide + Insulin Glargine v Insulin Lispro + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[22]

P-value

< 0.0001

Method

t-test, 1-sided

Parameter type

Mean difference (net)

Point estimate

0.06

Confidence interval

level

95%

sides

2-sided

lower limit

-0.05

upper limit

0.17

Notes
[22] - Difference in change from Baseline least squares means (albiglutide - insulin lispro) is greater than 0.30% based on one-sided t-test with 0.025 level of significance

Secondary: Change from Baseline in Fasting plasma glucose (FPG) at Week 26

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End point title

Change from Baseline in Fasting plasma glucose (FPG) at Week 26

End point description

FPG was measured at Baseline (Day -1). FPG values for all participants at Week 26 were not collected due to an error in the protocol and were imputed with the fasting serum glucose (FSG) values at this time point. The imputation of the FPG at Week 26 from the FSG values was deemed acceptable from the results of the analysis of the correlation between FPG and FSG at the screening visit. The Baseline value was the last available non-missing value prior to the first dose of the randomized treatment, thus Baseline was Day -1. Change from Baseline is defined as the post-Baseline value minus the Baseline value.

End point type

Secondary

End point timeframe

Baseline and Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	345 ^[23]	349 ^[24]
Units: Millimoles per Liter
least squares mean (standard error)
Millimoles per Liter	-2.01 ± 0.120	-1.46 ± 0.121

Notes
[23] - FA Population. Only those participants available at the specified time points were analyzed.
[24] - FA Population. Only those participants available at the specified time points were analyzed.

Statistical analysis 1

Statistical analysis description

Least square mean difference (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented.

Comparison groups

Insulin Lispro + Insulin Glargine v Albiglutide + Insulin Glargine

Number of subjects included in analysis

694

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0004

Method

t-test, 2-sided

Parameter type

Mean difference (net)

Point estimate

-0.55

Confidence interval

level

95%

sides

2-sided

lower limit

-0.86

upper limit

-0.25

Secondary: Change from Baseline to Week 26 in FPG

Top of page

End point title

Change from Baseline to Week 26 in FPG

End point description

FPG was measured at Baseline (Day -1) up to Week 26. FPG values for all participants at Week 26 were not collected due to an error in the protocol and were imputed with the FSG values at this time point. The imputation of the FPG at Week 26 from the FSG values was deemed acceptable from the results of the analysis of the correlation between FPG and FSG at the screening visit. The Baseline value was the last available non-missing value prior to the first dose of the randomized treatment, thus Baseline was Day -1. Change from Baseline is defined as the post-Baseline value minus the Baseline value.

End point type

Secondary

End point timeframe

Baseline to Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	402 ^[25]	412 ^[26]
Units: Millimoles per Liter
least squares mean (standard error)
Week 4, n=356,371	-1.30 ± 0.119	-0.76 ± 0.118
Week 5, n=366,388	-1.07 ± 0.126	-0.88 ± 0.125
Week 18, n=348,353	-1.76 ± 0.124	-1.23 ± 0.124
Week 26, n=345,349	-2.01 ± 0.120	-1.46 ± 0.121

Notes
[25] - FA Population. Only those participants available at the specified time points were analyzed.
[26] - FA Population. Only those participants available at the specified time points were analyzed.

Statistical analysis 1

Statistical analysis description

Least square mean difference (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 4.

Comparison groups

Insulin Lispro + Insulin Glargine v Albiglutide + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.54

Confidence interval

level

95%

sides

2-sided

lower limit

-0.84

upper limit

-0.24

Statistical analysis 2

Statistical analysis description

Least square mean difference (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 5.

Comparison groups

Insulin Lispro + Insulin Glargine v Albiglutide + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.19

Confidence interval

level

95%

sides

2-sided

lower limit

-0.51

upper limit

0.13

Statistical analysis 3

Statistical analysis description

Least square mean difference (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 18.

Comparison groups

Insulin Lispro + Insulin Glargine v Albiglutide + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.53

Confidence interval

level

95%

sides

2-sided

lower limit

-0.85

upper limit

-0.22

Statistical analysis 4

Statistical analysis description

Least square mean difference (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 26.

Comparison groups

Insulin Lispro + Insulin Glargine v Albiglutide + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0004

Method

t-test, 2-sided

Parameter type

Mean difference (net)

Point estimate

-0.55

Confidence interval

level

95%

sides

2-sided

lower limit

-0.86

upper limit

-0.25

Secondary: Number of participants achieving HbA1c <7.0% at Week 26

Top of page

End point title

Number of participants achieving HbA1c <7.0% at Week 26

End point description

HbA1c is glycosylated hemoglobin. Number of participants achieving a HbA1c <7.0% at Week 26 are presented.

End point type

Secondary

End point timeframe

Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	402 ^[27]	412 ^[28]
Units: Participants
Participants	244	255

Notes
[27] - FA Population.
[28] - FA Population.

Statistical analysis 1

Statistical analysis description

Odds ratio (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented.

Comparison groups

Insulin Lispro + Insulin Glargine v Albiglutide + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7026 ^[29]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

1.31

Notes
[29] - Non-parametric Cochran-Mantel-Haenszel (CMH) test after adjusting for Baseline HbA1c category, age category, region and current use of metformin.

Secondary: Number of participants achieving HbA1c <7.0% up to Week 26

Top of page

End point title

Number of participants achieving HbA1c <7.0% up to Week 26

End point description

HbA1c is glycosylated hemoglobin. Number of participants achieving a HbA1c <7.0% up to Week 26 are presented.

End point type

Secondary

End point timeframe

Up to Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	402 ^[30]	412 ^[31]
Units: Participants
Week 4	142	139
Week 5	157	182
Week 10	220	261
Week 18	251	281
Week 26	244	255

Notes
[30] - FA Population.
[31] - FA Population.

Statistical analysis 1

Statistical analysis description

Odds ratio (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 4.

Comparison groups

Albiglutide + Insulin Glargine v Insulin Lispro + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2883 ^[32]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

1.17

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.64

Notes
[32] - Analysis was performed using non-parametric Cochran-Mantel-Haenszel (CMH) test after adjusting for baseline HbA1c category, age category, region and current use of metformin

Statistical analysis 2

Statistical analysis description

Odds ratio (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 5.

Comparison groups

Albiglutide + Insulin Glargine v Insulin Lispro + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3034 ^[33]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.59

upper limit

1.15

Notes
[33] - Analysis was performed using non-parametric Cochran-Mantel-Haenszel (CMH) test after adjusting for baseline HbA1c category, age category, region and current use of metformin.

Statistical analysis 3

Statistical analysis description

Odds ratio (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 10.

Comparison groups

Albiglutide + Insulin Glargine v Insulin Lispro + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0151 ^[34]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

0.71

Confidence interval

level

95%

sides

2-sided

lower limit

0.52

upper limit

0.98

Notes
[34] - Analysis was performed using non-parametric Cochran-Mantel-Haenszel (CMH) test after adjusting for baseline HbA1c category, age category, region and current use of metformin.

Statistical analysis 4

Statistical analysis description

Odds ratio (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 18.

Comparison groups

Albiglutide + Insulin Glargine v Insulin Lispro + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0518 ^[35]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

0.75

Confidence interval

level

95%

sides

2-sided

lower limit

0.54

upper limit

1.03

Notes
[35] - Analysis was performed using non-parametric Cochran-Mantel-Haenszel (CMH) test after adjusting for baseline HbA1c category, age category, region and current use of metformin

Statistical analysis 5

Statistical analysis description

Odds ratio (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 26.

Comparison groups

Albiglutide + Insulin Glargine v Insulin Lispro + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7026 ^[36]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

1.31

Notes
[36] - Analysis was performed using non-parametric Cochran-Mantel-Haenszel (CMH) test after adjusting for baseline HbA1c category, age category, region and current use of metformin

Secondary: Number of participants achieving a HbA1c <6.5% at Week 26

Top of page

End point title

Number of participants achieving a HbA1c <6.5% at Week 26

End point description

Number of participants achieving a HbA1c <6.5% at Week 26 are presented.

End point type

Secondary

End point timeframe

Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	402 ^[37]	412 ^[38]
Units: Participants
Participants	147	169

Notes
[37] - FA Population.
[38] - FA Population.

Statistical analysis 1

Statistical analysis description

Odds ratio (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented.

Comparison groups

Insulin Lispro + Insulin Glargine v Albiglutide + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2298 ^[39]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.63

upper limit

1.17

Notes
[39] - Analysis was performed using non-parametric Cochran-Mantel-Haenszel (CMH) test after adjusting for baseline HbA1c category, age category, region and current use of metformin.

Secondary: Number of participants achieving a HbA1c <6.5% up to Week 26

Top of page

End point title

Number of participants achieving a HbA1c <6.5% up to Week 26

End point description

Number of participants achieving a HbA1c <6.5% up to Week 26 are presented.

End point type

Secondary

End point timeframe

Up to Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	402 ^[40]	412 ^[41]
Units: Participants
Week 4	39	33
Week 5	63	62
Week 10	116	140
Week 18	150	178
Week 26	147	169

Notes
[40] - FA Population.
[41] - FA Population.

Statistical analysis 1

Statistical analysis description

Odds ratio (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 4.

Comparison groups

Albiglutide + Insulin Glargine v Insulin Lispro + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2143 ^[42]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

1.32

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

2.23

Notes
[42] - Analysis was performed using non-parametric Cochran-Mantel-Haenszel (CMH) test after adjusting for baseline HbA1c category, age category, region and current use of metformin.

Statistical analysis 2

Statistical analysis description

Odds ratio (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 5.

Comparison groups

Albiglutide + Insulin Glargine v Insulin Lispro + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4703 ^[43]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

1.24

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

1.91

Notes
[43] - Analysis was performed using non-parametric Cochran-Mantel-Haenszel (CMH) test after adjusting for baseline HbA1c category, age category, region and current use of metformin.

Statistical analysis 3

Statistical analysis description

Odds ratio (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 10.

Comparison groups

Albiglutide + Insulin Glargine v Insulin Lispro + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2139 ^[44]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.58

upper limit

1.14

Notes
[44] - Analysis was performed using non-parametric Cochran-Mantel-Haenszel (CMH) test after adjusting for baseline HbA1c category, age category, region and current use of metformin.

Statistical analysis 4

Statistical analysis description

Odds ratio (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 18.

Comparison groups

Albiglutide + Insulin Glargine v Insulin Lispro + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.079 ^[45]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.59

upper limit

1.11

Notes
[45] - Analysis was performed using non-parametric Cochran-Mantel-Haenszel (CMH) test after adjusting for baseline HbA1c category, age category, region and current use of metformin.

Statistical analysis 5

Statistical analysis description

Odds ratio (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 26.

Comparison groups

Albiglutide + Insulin Glargine v Insulin Lispro + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2298 ^[46]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.63

upper limit

1.17

Notes
[46] - Analysis was performed using non-parametric Cochran-Mantel-Haenszel (CMH) test after adjusting for baseline HbA1c category, age category, region and current use of metformin.

Secondary: Number of participants who met prespecified criteria for severe, persistent hyperglycemia at Week 26

Top of page

End point title

Number of participants who met prespecified criteria for severe, persistent hyperglycemia at Week 26

End point description

Meeting prespecified criteria for severe, persistent hyperglycemia was defined operationally as being withdrawn due to lack of efficacy as recorded on the Treatment Discontinuation and Study Conclusion electronic case report form pages. Number of participants who met prespecified criteria for severe, persistent hyperglycemia at Week 26 are presented.

End point type

Secondary

End point timeframe

Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	402 ^[47]	412 ^[48]
Units: Participants
Participants	3	3

Notes
[47] - FA Population.
[48] - FA Population.

Statistical analysis 1

Statistical analysis description

Odds ratio (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented

Comparison groups

Albiglutide + Insulin Glargine v Insulin Lispro + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8292 ^[49]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

1.08

Confidence interval

level

95%

sides

2-sided

lower limit

0.24

upper limit

4.77

Notes
[49] - Analysis was performed using non-parametric Cochran-Mantel-Haenszel (CMH) test after adjusting for baseline HbA1c category, age category, region and current use of metformin.

Secondary: Number of participants meeting prespecified criteria for severe, persistent hyperglycemia up to Week 26

Top of page

End point title

Number of participants meeting prespecified criteria for severe, persistent hyperglycemia up to Week 26

End point description

Meeting prespecified criteria for severe, persistent hyperglycemia was defined operationally as being withdrawn due to lack of efficacy as recorded on the Treatment Discontinuation and Study Conclusion electronic case report form pages. Number of participants meeting prespecified criteria for severe, persistent hyperglycemia up to Week 26 are presented.

End point type

Secondary

End point timeframe

Up to Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	402 ^[50]	412 ^[51]
Units: Participants
0 to <=4 Weeks	0	0
>4 to <=5 Weeks	0	0
>5 to <=10 Weeks	2	0
>10 to <=18 Weeks	0	1
>18 to <=26 Weeks	1	2

Notes
[50] - FA Population.
[51] - FA Population.

No statistical analyses for this end point

Secondary: Total daily insulin dose at Week 4, Week 10 and Week 18

Top of page

End point title

Total daily insulin dose at Week 4, Week 10 and Week 18

End point description

Based on MMRM model, prescribed total daily basal insulin dose was equal to Baseline prescribed total daily basal insulin dose + treatment + Baseline HbA1c category + region + age category + current use of metformin + visit week + treatment-by-visit week interaction + Baseline prescribed total daily basal insulin dose-by-visit week interaction. Total daily insulin dose at Week 4, Week 10 and Week 18 is presented. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.

End point type

Secondary

End point timeframe

Weeks 4, 10, and 18

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	402 ^[52]	412 ^[53]
Units: International Units
least squares mean (standard error)
Week 4, n=388,403	50.53 ± 1.183	106.91 ± 1.187
Week 10, n=375,386	57.99 ± 1.597	121.69 ± 1.589
Week 18, n=359,361	68.23 ± 2.010	130.22 ± 1.998

Notes
[52] - FA Population.
[53] - FA Population.

Statistical analysis 1

Statistical analysis description

Least square mean difference (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 4.

Comparison groups

Insulin Lispro + Insulin Glargine v Albiglutide + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-56.38

Confidence interval

level

95%

sides

2-sided

lower limit

-59.19

upper limit

-53.57

Statistical analysis 2

Statistical analysis description

Least square mean difference (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 10.

Comparison groups

Insulin Lispro + Insulin Glargine v Albiglutide + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-63.7

Confidence interval

level

95%

sides

2-sided

lower limit

-67.78

upper limit

-59.62

Statistical analysis 3

Statistical analysis description

Least square mean difference (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 18.

Comparison groups

Insulin Lispro + Insulin Glargine v Albiglutide + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-62

Confidence interval

level

95%

sides

2-sided

lower limit

-67.29

upper limit

-56.7

Secondary: Total daily basal insulin (insulin glargine) at Week 4, 10, 18, and 26 visits

Top of page

End point title

Total daily basal insulin (insulin glargine) at Week 4, 10, 18, and 26 visits

End point description

Based on MMRM model, prescribed total daily basal insulin dose was equal to Baseline prescribed total daily basal insulin dose + treatment + Baseline HbA1c category + region + age category + current use of metformin + visit week + treatment-by-visit week interaction + Baseline prescribed total daily basal insulin dose-by-visit week interaction. Total daily basal insulin (insulin glargine) at Week 4, 10, 18, and 26 visits is presented. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.

End point type

Secondary

End point timeframe

Weeks 4, 10, 18, and 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	402 ^[54]	412 ^[55]
Units: International Units
least squares mean (standard error)
Week 4, n=388,403	49.97 ± 0.534	50.94 ± 0.536
Week 10, n=375,386	56.14 ± 0.767	55.79 ± 0.761
Week 18, n=359,361	59.42 ± 0.928	59.18 ± 0.920
Week 26, n=342,341	59.83 ± 0.996	59.43 ± 0.988

Notes
[54] - FA Population.
[55] - FA Population.

Statistical analysis 1

Statistical analysis description

Least square mean difference (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 4.

Comparison groups

Albiglutide + Insulin Glargine v Insulin Lispro + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Mean difference (final values)

Point estimate

-0.97

Confidence interval

level

95%

sides

2-sided

lower limit

-2.25

upper limit

0.3

Statistical analysis 2

Statistical analysis description

Least square mean difference (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 10.

Comparison groups

Albiglutide + Insulin Glargine v Insulin Lispro + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

0.34

Confidence interval

level

95%

sides

2-sided

lower limit

-1.64

upper limit

2.33

Statistical analysis 3

Statistical analysis description

Least square mean difference (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 18.

Comparison groups

Albiglutide + Insulin Glargine v Insulin Lispro + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

0.24

Confidence interval

level

95%

sides

2-sided

lower limit

-2.21

upper limit

2.69

Statistical analysis 4

Statistical analysis description

Least square mean difference (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 26.

Comparison groups

Albiglutide + Insulin Glargine v Insulin Lispro + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7699

Method

t-Test, 2-sided

Parameter type

Mean difference (final values)

Point estimate

0.39

Confidence interval

level

95%

sides

2-sided

lower limit

-2.25

upper limit

3.04

Secondary: Total daily bolus insulin (insulin lispro) at Week 4, 10, 18, and 26 visits

Top of page

End point title

Total daily bolus insulin (insulin lispro) at Week 4, 10, 18, and 26 visits

End point description

Based on MMRM model, prescribed total daily basal insulin dose was equal to Baseline prescribed total daily basal insulin dose + treatment + Baseline HbA1c category + region + age category + current use of metformin + visit week + treatment-by-visit week interaction + Baseline prescribed total daily basal insulin dose-by-visit week interaction. Total daily bolus insulin (insulin lispro) at Week 4, 10, 18, and 26 visits is presented. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.

End point type

Secondary

End point timeframe

Weeks 4, 10, 18, and 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	402 ^[56]	412 ^[57]
Units: International Units
least squares mean (standard error)
Week 4, n=388,403	0.62 ± 0.887	56.67 ± 0.892
Week 10, n=375,386	1.90 ± 1.147	66.66 ± 1.144
Week 18, n=359,361	8.89 ± 1.436	71.81 ± 1.430
Week 26, n=342,341	10.64 ± 1.523	72.47 ± 1.517

Notes
[56] - FA Population.
[57] - FA Population.

Statistical analysis 1

Statistical analysis description

Least square mean difference (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 4.

Comparison groups

Insulin Lispro + Insulin Glargine v Albiglutide + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-56.05

Confidence interval

level

95%

sides

2-sided

lower limit

-58.17

upper limit

-53.94

Statistical analysis 2

Statistical analysis description

Least square mean difference (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 10.

Comparison groups

Insulin Lispro + Insulin Glargine v Albiglutide + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-64.76

Confidence interval

level

95%

sides

2-sided

lower limit

-67.68

upper limit

-61.85

Statistical analysis 3

Statistical analysis description

Least square mean difference (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 18.

Comparison groups

Insulin Lispro + Insulin Glargine v Albiglutide + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-62.92

Confidence interval

level

95%

sides

2-sided

lower limit

-66.69

upper limit

-59.15

Statistical analysis 4

Statistical analysis description

Least square mean difference (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented for Week 26.

Comparison groups

Insulin Lispro + Insulin Glargine v Albiglutide + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

t-test, 2-sided

Parameter type

Mean difference (final values)

Point estimate

-61.83

Confidence interval

level

95%

sides

2-sided

lower limit

-65.85

upper limit

-57.81

Secondary: Total number of weekly insulin injections to achieve glycemic control at Baseline/Randomization and Week 4, 10, 18, and 26

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End point title

Total number of weekly insulin injections to achieve glycemic control at Baseline/Randomization and Week 4, 10, 18, and 26

End point description

Total number of weekly insulin injections (7 days) to achieve glycemic control at Baseline/Randomization and Week 4, 10, 18, and 26 are presented. Only those participants available at the specified time points were analyzed represented by n=X,X in category titles.

End point type

Secondary

End point timeframe

Baseline (Day -1) and Weeks 4, 10, 18 and 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	402 ^[58]	412 ^[59]
Units: Insulin Injections
arithmetic mean (standard deviation)
Baseline, n=401,412	28.79 ± 1.470	28.00 ± 0.000
Week 4, n=388,403	8.11 ± 1.506	28.00 ± 0.000
Week 10, n=375,386	9.06 ± 3.121	28.00 ± 0.000
Week 18, n=359,361	12.62 ± 7.330	28.00 ± 0.000
Week 26, n=342,341	13.22 ± 7.758	28.00 ± 0.000

Notes
[58] - FA Population.
[59] - FA Population.

No statistical analyses for this end point

Secondary: Percentage of participants achieving HbA1c <7.0% without weight gain at Week 26

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End point title

Percentage of participants achieving HbA1c <7.0% without weight gain at Week 26

End point description

Percentage of participants achieving HbA1c <7.0% without weight gain are presented.

End point type

Secondary

End point timeframe

Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	402 ^[60]	412 ^[61]
Units: Percentage of participants
number (not applicable)
Percentage of participants	49.8	21.4

Notes
[60] - FA Population.
[61] - FA Population.

Statistical analysis 1

Statistical analysis description

Odds ratio (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented.

Comparison groups

Insulin Lispro + Insulin Glargine v Albiglutide + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.0001 ^[62]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

3.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.52

upper limit

4.86

Notes
[62] - Analysis was performed using non-parametric Cochran-Mantel-Haenszel (CMH) test after adjusting for baseline HbA1c category, age category, region and current use of metformin.

Secondary: Percentage of participants achieving HbA1c <7.0% without severe or documented symptomatic hypoglycemia at Week 26

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End point title

Percentage of participants achieving HbA1c <7.0% without severe or documented symptomatic hypoglycemia at Week 26

End point description

Percentage of participants achieving HbA1c <7.0% without severe or documented symptomatic hypoglycemia are presented.

End point type

Secondary

End point timeframe

Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	402 ^[63]	412 ^[64]
Units: Percentage of participants
number (not applicable)
Percentage of participants	21.1	9.5

Notes
[63] - FA Population.
[64] - FA Population.

Statistical analysis 1

Statistical analysis description

Odds ratio (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented.

Comparison groups

Insulin Lispro + Insulin Glargine v Albiglutide + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.0001 ^[65]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

2.36

Confidence interval

level

95%

sides

2-sided

lower limit

1.54

upper limit

3.6

Notes
[65] - Analysis was performed using non-parametric Cochran-Mantel-Haenszel (CMH) test after adjusting for baseline HbA1c category, age category, region and current use of metformin.

Secondary: Percentage of participants achieving HbA1c <7.0% without weight gain and without severe or documented hypoglycemia at Week 26

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End point title

Percentage of participants achieving HbA1c <7.0% without weight gain and without severe or documented hypoglycemia at Week 26

End point description

Percentage of participants achieving HbA1c <7.0% without weight gain and without severe or documented hypoglycemia are presented.

End point type

Secondary

End point timeframe

Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	402 ^[66]	412 ^[67]
Units: Percentage of participants
number (not applicable)
Percentage of participants	15.9	3.9

Notes
[66] - FA Population.
[67] - FA Population.

Statistical analysis 1

Statistical analysis description

Odds ratio (albiglutide + insulin glargine minus insulin lispro + insulin glargine) has been presented.

Comparison groups

Insulin Lispro + Insulin Glargine v Albiglutide + Insulin Glargine

Number of subjects included in analysis

814

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.0001 ^[68]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

3.78

Confidence interval

level

95%

sides

2-sided

lower limit

2.21

upper limit

6.48

Notes
[68] - Analysis was performed using non-parametric Cochran-Mantel-Haenszel (CMH) test after adjusting for baseline HbA1c category, age category, region and current use of metformin.

Secondary: Number of participants with on-therapy adverse events (AE) and serious AE (SAE), and AE leading to discontinuation of randomized study medication

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End point title

Number of participants with on-therapy adverse events (AE) and serious AE (SAE), and AE leading to discontinuation of randomized study medication

End point description

AE is any untoward medical occurrence in a participant, temporally associated with use of medicinal product (MP), whether or not considered related to MP. AE can be any unfavorable, unintended sign (also an abnormal laboratory finding), symptom, or disease (new/exacerbated) temporally associated with use of MP. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, or is a congenital anomaly/birth defect or is medically significant or all events of possible drug induced liver injury with hyperbilirubinemia. Safety Population: All participants who received at least 1 dose of randomized study medication. A participant randomized to Albiglutide + Insulin glargine by mistake received Insulin Lispro + Insulin Glargine instead. Since this participant received actual treatment as Insulin Lispro + Insulin Glargine, was summarized as such in Safety Population.

End point type

Secondary

End point timeframe

Up to Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	400 ^[69]	413 ^[70]
Units: Participants
AE	261	254
SAE	23	31
AE leading to study medication discontinuation	12	6

Notes
[69] - Safety Population.
[70] - Safety Population.

No statistical analyses for this end point

Secondary: Number of participants with other AE of special interest

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End point title

Number of participants with other AE of special interest

End point description

AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with use of a MP, whether or not considered related to MP. AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with use of MP. AE of special interest included hypoglycemic events, cardiovascular events, gastrointestinal events, injection site reactions, potential systemic allergic reactions, pancreatitis, pancreatic cancer, malignant neoplasms following treatment with insulin, diabetic retinopathy events, appendicitis, liver events, pneumonia, and atrial fibrillation/flutter.

End point type

Secondary

End point timeframe

Up to Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	400 ^[71]	413 ^[72]
Units: Participants
Hypoglycemic Events	305	361
Cardiovascular Events	7	9
Gastrointestinal Events	102	53
Injection Site Reactions	8	1
Systemic Allergic Reactions	3	0
Pancreatitis	1	0
Pancreatic cancer	0	0
Malignant Neoplasm	2	2
Diabetic Retinopathy	4	17
Appendicitis	1	0
Liver Events	0	2
Pneumonia	1	3
Atrial Fibrillation/Flutter	4	1

Notes
[71] - Safety Population.
[72] - Safety Population.

No statistical analyses for this end point

Secondary: Percentage of participants with events of hypoglycemia with confirmed home blood glucose monitoring and/or third-party intervention through Week 26

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End point title

Percentage of participants with events of hypoglycemia with confirmed home blood glucose monitoring and/or third-party intervention through Week 26

End point description

Hypoglycemic events with confirmed home plasma glucose monitoring <3.9 millimoles per Liter and/or requiring third party intervention were severe, documented symptomatic (DS) and asymptomatic hypoglycemic events. Participants with more than one hypoglycemic event are counted in all categories reported. Any severe, documented symptomatic, and asymptomatic hypoglycemic events in 3-month intervals (i.e., from Day 0 to Week 12, >Week 12 to Week 26) are presented.

End point type

Secondary

End point timeframe

Up to Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	400	413
Units: Percentage of participants
number (not applicable)
Any event: Onset date falls under 0 to <= 12 weeks	55.3	79.2
Any event: Onset date falls > 12 to <= 26 Weeks	60.3	79.4
Severe: Onset date falls under 0 to <= 12 weeks	1.8	3.6
Severe: Onset date falls > 12 to <= 26 Weeks	0.8	1.9
DS: Onset date falls under 0 to <= 12 weeks	33.8	63.0
DS: Onset date falls > 12 to <= 26 Weeks	40.8	62.0
Asymptomatic: Onset date under 0 to <= 12 weeks	38.3	56.9
Asymptomatic: Onset date falls > 12 to <= 26 Weeks	44.3	54.7

No statistical analyses for this end point

Secondary: Number of participants with hypoglycemic events (in total and by each category as defined by the American Diabetes Association criteria)

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End point title

Number of participants with hypoglycemic events (in total and by each category as defined by the American Diabetes Association criteria)

End point description

The American Diabetes Association has categorized hypoglycemic events as follows: Severe, documented symptomatic, asymptomatic, probably symptomatic and pseudohypoglycemia. Number of participants with hypoglycemic events in total are also presented.

End point type

Secondary

End point timeframe

Up to Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	400 ^[73]	413 ^[74]
Units: Participants
Severe	9	22
Documented Symptomatic	203	299
Asymptomatic	230	293
Probably Symptomatic	29	52
Pseudohypoglycemia	45	83
Missing	9	13
Total	305	361

Notes
[73] - Safety Population.
[74] - Safety Population.

No statistical analyses for this end point

Secondary: Number of participants with daytime and nocturnal hypoglycemia

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End point title

Number of participants with daytime and nocturnal hypoglycemia

End point description

Daytime hypoglycemia was defined as hypoglycemic events with an onset between 06:00 hours and 00:00 hours (inclusive), and nocturnal hypoglycemia (in total and by category), defined as hypoglycemic events with an onset between 00:01 hours and 05:59 hours (inclusive). Number of participants with daytime and nocturnal hypoglycemia (in total and by category) are presented.

End point type

Secondary

End point timeframe

Up to Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	400 ^[75]	413 ^[76]
Units: Participants
Any (Total) Daytime Hypoglycemic Event	288	356
Any (Total) Nocturnal Hypoglycemic Event	155	225
Severe Daytime Hypoglycemic Event	6	14
Severe Nocturnal Hypoglycemic Event	4	6
Documented Symptomatic Daytime Hypoglycemic event	187	293
Documented Symptomatic Nocturnal Hypoglycemia	101	152
Asymptomatic Daytime Hypoglycemic event	217	281
Asymptomatic Nocturnal Hypoglycemic event	77	106
Probably Symptomatic Daytime Hypoglycemic event	22	4
Probably Symptomatic Nocturnal Hypoglycemic event	7	21
Pseudohypoglycemia Daytime Hypoglycemic event	36	70
Pseudohypoglycemia Nocturnal Hypoglycemic event	17	34
Missing Daytime Hypoglycemic Event	9	11
Mising Nocturnal Hypoglycemic Event	2	4

Notes
[75] - Safety Population.
[76] - Safety Population.

No statistical analyses for this end point

Secondary: Number of participants with hypoglycemia with blood glucose <56 milligrams per deciliter (mg/dL) (<3.1 millimoles per liter [mmol/L]), regardless of symptoms

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End point title

Number of participants with hypoglycemia with blood glucose <56 milligrams per deciliter (mg/dL) (<3.1 millimoles per liter [mmol/L]), regardless of symptoms

End point description

Number of participants with hypoglycemia with blood glucose <56 mg/dL (<3.1 mmol/L), regardless of symptoms are presented.

End point type

Secondary

End point timeframe

Up to Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	400 ^[77]	413 ^[78]
Units: Participants
Participants	141	239

Notes
[77] - Safety Population.
[78] - Safety Population.

No statistical analyses for this end point

Secondary: Number of participants with hematology values of clinical concern

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End point title

Number of participants with hematology values of clinical concern

End point description

Hematology parameters included basophils, eosinophils, hematocrit, hemoglobin, lymphocytes, monocytes, neutrophils, neutrophil bands, platelets, red blood cell (RBC) count, segmented neutrophils and white blood cell (WBC) count. The potential clinical concern values were: Hematocrit >0.05 below lower limit of normal (LLN) and >0.04 above upper limit of normal (ULN), hemoglobin: >20 grams cells per Liter (g/L) below LLN and >10 g/L above ULN, lymphocytes: <0.5 x LLN, neutrophils: <1 giga cells per liter (GI/L), platelets: <80 GI/L and >500 GI/L, segmented neutrophils: <0.5 x LLN, RBC count: >1 GI/L below LLN and >5 GI/L above ULN and none for basophils, eosinophils, monocytes, neutrophil bands and RBC count. Only those parameters for which at least one value of potential clinical concern was reported are summarized.

End point type

Secondary

End point timeframe

Up to 30 weeks

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	394 ^[79]	407 ^[80]
Units: Participants
Hematocrit: >0.05 (fraction) below LLN	5	6
Hematocrit: >0.04 (fraction) above ULN	9	12
Hemoglobin: >20 g/L below LLN	9	9
Hemoglobin: >10 g/L above ULN	2	3
Leukocytes: >1 GI/L below LLN	1	1
Leukocytes: >5 GI/L above ULN	4	1
Neutrophils: <1 GI/L	2	3
Neutrophils, Segmented: <0.5 x LLN	2	3
Platelets: <80 GI/L	1	1
Platelets: >500 GI/L	3	1

Notes
[79] - Safety Population. Only those participants available at the specified time points were analyzed.
[80] - Safety Population. Only those participants available at the specified time points were analyzed.

No statistical analyses for this end point

Secondary: Number of participants with clinical chemistry values of clinical concern

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End point title

Number of participants with clinical chemistry values of clinical concern

End point description

Clinical chemistry parameters and their potential clinical concern values were: albumin (>5 g/L above ULN or below LLN), alkaline phosphatase(>3 x ULN), alanine aminotransferase (>3 x ULN), aspartate aminotransferase (>3 x ULN), carbon dioxide content (<16 millimoles per Liter [mmol/L] and > 40 mmol/L), blood urea nitrogen (>2 x ULN), calcium (<1.8 mmol/L and >3.0 mmol/L), chloride (none), creatinine (>159 micromoles/Liter), direct bilirubin (>1.35 x ULN), gamma glutamyl transferase (>3 x ULN), glucose (fasting) (<3 mmol/L and >22 mmol/L), magnesium (<0.411 mmol/L and >1.644 mmol/L), phosphate (>0.323 mmol/L above ULN or below LLN), potassium (>0.5 mmol/L below LLN and >1.0 mmol/L above ULN), sodium (>5 mmol/L above ULN or below LLN), triglycerides (> 9.04 mmol/L), total bilirubin (>1.5 x ULN), total protein (>15 g/L above ULN or below LLN) and uric acid (>654 umol/L). Only those parameters for which at least one value of potential clinical concern was reported are summarized.

End point type

Secondary

End point timeframe

Up to 30 weeks

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	400 ^[81]	413 ^[82]
Units: Participants
Fasting Serum Glucose: <3 mmol/L, n= 394,405	12	16
Fasting Serum Glucose: >22 mmol/L, n= 394,405	0	1
Fasting Plasma Glucose: <3 mmol/L, n= 388,406	9	14
Fasting Plasma Glucose: >22 mmol/L, n= 388,406	1	0
Albumin: >5 g/L below LLN, n=394,407	0	0
Albumin: >5 g/L above ULN, n=394,407	0	0
Calcium: <1.8 mmol/L, n=394,407	1	1
Calcium: >3.0 mmol/L, n=394,407	0	0
Carbon Dioxide: <16 mmol/L, n=394,407	5	8
Carbon Dioxide: >40 mmol/L, n=394,407	0	0
Magnesium: <0.411 mmol/L, n=394,407	1	1
Magnesium: >1.644 mmol/L, n=394,407	0	0
Phosphate: >0.323 mmol/L below LLN, n=394,407	0	0
Phosphate: >0.323 mmol/L above ULN, n=394,407	2	4
Potassium: >0.5 mmol/L below LLN, n=394,407	1	0
Potassium: >1.0 mmol/L above ULN, n=394,407	0	1
Protein: >15 g/L below LLN, n=394,407	0	0
Protein: >15 g/L above ULN, n=394,407	0	0
Sodium: >5 mmol/L below LLN, n=394,407	1	0
Sodium: >5 mmol/L above ULN, n=394,407	1	0
Triglycerides: >9.04 mmol/L, n=393,405	7	1
Urate: >654 μmol/L, n=394,407	0	2
Urea: >2 x ULN, n=394,407	2	1
Alanine Aminotransferase: >3 x ULN, n=396,410	0	5
Alkaline Phosphatase: >3 x ULN, n=396,410	1	0
Aspartate Aminotransferase: >3 x ULN, n=396,410	0	2
Bilirubin: >1.5 x ULN, n=396,410	1	1
Creatinine: >159 μmol/L, n=396,410	20	16
Direct Bilirubin: >1.35 x ULN, n=396,410	0	1
Gamma Glutamyl Transferase: >3 x ULN, n=396,410	14	14

Notes
[81] - Safety Population. Only those participants available at the specified time points were analyzed.
[82] - Safety Population. Only those participants available at the specified time points were analyzed.

No statistical analyses for this end point

Secondary: Mean urine albumin/creatinine ratio at Week 0 and Week 26

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End point title

Mean urine albumin/creatinine ratio at Week 0 and Week 26

End point description

Urine samples were collected for analysis of albumin/creatinine ratio. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles. Mean urine albumin/creatinine ratio at Week 0 and Week 26 are presented.

End point type

Secondary

End point timeframe

Week 0 and Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	400 ^[83]	413 ^[84]
Units: Grams per mole
arithmetic mean (standard deviation)
Week 0, n=369,376	14.40 ± 49.884	11.57 ± 31.089
Week 26, n=317,324	10.37 ± 32.992	11.55 ± 31.975

Notes
[83] - Safety Population.
[84] - Safety Population.

No statistical analyses for this end point

Secondary: Mean albumin at Week 0 and Week 26

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End point title

Mean albumin at Week 0 and Week 26

End point description

Urine samples were collected for analysis of albumin. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles. Mean albumin at Week 0 and Week 26 are presented.

End point type

Secondary

End point timeframe

Week 0 and Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	400 ^[85]	413 ^[86]
Units: Milligrams per Liter
arithmetic mean (standard deviation)
Week 0, n=394,405	127.7 ± 428.46	108.2 ± 301.88
Week 26, n=348,345	110.5 ± 375.41	146.3 ± 628.73

Notes
[85] - Safety Population.
[86] - Safety Population.

No statistical analyses for this end point

Secondary: Mean creatinine at Week 0 and Week 26

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End point title

Mean creatinine at Week 0 and Week 26

End point description

Urine samples were collected for analysis of creatinine. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles. Mean creatinine at Week 0 and Week 26 are presented.

End point type

Secondary

End point timeframe

Week 0 and Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	400 ^[87]	413 ^[88]
Units: Micromoles per Liter
arithmetic mean (standard deviation)
Week 0, n=395,406	10646.3 ± 5190.43	10663.8 ± 5639.54
Week 26, n=350,345	11364.6 ± 5998.72	11394.2 ± 5663.72

Notes
[87] - Safety Population.
[88] - Safety Population.

No statistical analyses for this end point

Secondary: Mean specific gravity at Week 0 and Week 26

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End point title

Mean specific gravity at Week 0 and Week 26

End point description

Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney’s ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. A urinary specific gravity measurement is a routine part of urinalysis. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.

End point type

Secondary

End point timeframe

Week 0 and Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	400 ^[89]	413 ^[90]
Units: Ratio
arithmetic mean (standard deviation)
Week 0, n=388,402	1.0182 ± 0.00599	1.0180 ± 0.00588
Week 26, n=347,343	1.0180 ± 0.00627	1.0186 ± 0.00588

Notes
[89] - Safety Population.
[90] - Safety Population.

No statistical analyses for this end point

Secondary: Number of participants with different values of potential of hydrogen (pH) at Week 0 and Week 26

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End point title

Number of participants with different values of potential of hydrogen (pH) at Week 0 and Week 26

End point description

Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0). Safety Population was analyzed. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.

End point type

Secondary

End point timeframe

Week 0 and Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	400 ^[91]	413 ^[92]
Units: Participants
pH=5; Week 0, n=388,402	92	107
pH=5.5; Week 0, n=388,402	132	132
pH=6; Week 0, n=388,402	86	77
pH=6.5; Week 0, n=388,402	29	43
pH=7; Week 0, n=388,402	29	24
pH=7.5; Week 0, n=388,402	13	11
pH=8; Week 0, n=388,402	6	7
pH=8.5; Week 0, n=388,402	1	1
pH=5; Week 26, n=347,343	80	100
pH=5.5; Week 26, n=347,343	107	104
pH=6; Week 26, n=347,343	69	70
pH=6.5; Week 26, n=347,343	42	23
pH=7; Week 26, n=347,343	19	23
pH=7.5; Week 26, n=347,343	17	18
pH=8; Week 26, n=347,343	7	5
pH=8.5; Week 26, n=347,343	5	0
pH>9; Week 26, n=347,343	1	0

Notes
[91] - Safety Population.
[92] - Safety Population.

No statistical analyses for this end point

Secondary: Number of participants with different number of erythrocytes in urine at Week 0 and Week 26

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End point title

Number of participants with different number of erythrocytes in urine at Week 0 and Week 26

End point description

Urine samples were collected for analysis of erythrocyte count. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles. Number of participants with different number of erythrocytes in urine at Week 0 and Week 26 are presented.

End point type

Secondary

End point timeframe

Week 0 and Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	400 ^[93]	413 ^[94]
Units: Participants
None Seen; Week 0, n=171,187	119	101
0 to 1; Week 0, n=171,187	34	51
1 to 3; Week 0, n=171,187	9	14
3 to 5; Week 0, n=171,187	3	12
5 to 10; Week 0, n=171,187	2	4
10 to 15; Week 0, n=171,187	0	2
15 to 25; Week 0, n=171,187	2	1
50 to 100; Week 0, n=171,187	0	1
>100; Week 0, n=171,187	2	1
None Seen; Week 26, n=166,144	98	79
0 to 1; Week 26, n=166,144	48	36
1 to 3; Week 26, n=166,144	8	19
3 to 5; Week 26, n=166,144	4	3
5 to 10; Week 26, n=166,144	4	4
25 to 50; Week 26, n=166,144	1	2
50 to 100; Week 26, n=166,144	2	0
>100; Week 26, n=166,144	1	1

Notes
[93] - Safety Population.
[94] - Safety Population.

No statistical analyses for this end point

Secondary: Number of participants with different number of leukocytes in urine at Week 0 and Week 26

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End point title

Number of participants with different number of leukocytes in urine at Week 0 and Week 26

End point description

Urine samples were collected for analysis of leukocyte count. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles. Number of participants with different number of leukocytes in urine at Week 0 and Week 26 are presented.

End point type

Secondary

End point timeframe

Week 0 and Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	400 ^[95]	413 ^[96]
Units: Participants
None Seen; Week 0, n=171,187	69	67
0 to 1; Week 0, n=171,187	27	31
1 to 3; Week 0, n=171,187	20	18
3 to 5; Week 0, n=171,187	16	13
5 to 10; Week 0, n=171,187	17	19
10 to 15; Week 0, n=171,187	7	6
15 to 25; Week 0, n=171,187	5	11
25 to 50; Week 0, n=171,187	5	11
50 to 100; Week 0, n=171,187	1	7
>100; Week 0, n=171,187	4	3
Innumerable; Week 0, n=171,187	0	1
None Seen; Week 26, n=166,144	65	44
0 to 1; Week 26, n=166,144	25	29
1 to 3; Week 26, n=166,144	22	20
3 to 5; Week 26, n=166,144	10	15
5 to 10; Week 26, n=166,144	22	14
10 to 15; Week 26, n=166,144	8	5
15 to 25; Week 26, n=166,144	3	3
20 to 50; Week 26, n=166,144	0	1
25 to 50; Week 26, n=166,144	5	6
50 to 100; Week 26, n=166,144	5	5
>100; Week 26, n=166,144	1	1
Innumerable; Week 26, n=166,144	0	1

Notes
[95] - Safety Population.
[96] - Safety Population.

No statistical analyses for this end point

Secondary: Change from Baseline in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), high density lipoprotein (HDL-c), triglycerides (TG) and free fatty acids (FFA) at Week 10 and Week 26

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End point title

Change from Baseline in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), high density lipoprotein (HDL-c), triglycerides (TG) and free fatty acids (FFA) at Week 10 and Week 26

End point description

Lipid parameters included TC, LDL-c, HDL-c, TG and FFA. The Baseline value was the last available non-missing value prior to the first dose of the randomized treatment, thus Baseline was Day -1. Change from Baseline is defined as the post-Baseline value minus the Baseline value. LDL-c and FFA were collected as part of the lipid panel and results were reviewed by investigators for individual participants. Change from Baseline at Week 10 and Week 26 was not assessed for these parameters. Analysis of these parameters was not a specific study objective and would not have any impact on study conclusions. Only those parameters with data values have been presented. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.

End point type

Secondary

End point timeframe

Baseline, Week 10 and Week 26

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	400 ^[97]	413 ^[98]
Units: Millimoles per Liters
arithmetic mean (standard deviation)
TC: Week 10, n=376,393	-0.244 ± 0.8047	0.041 ± 0.7425
TC: Week 26, n=348,351	-0.059 ± 0.8721	0.073 ± 0.8232
HDL-c: Week 10, n=376,393	-0.041 ± 0.1944	0.016 ± 0.1810
HDL-c: Week 26, n=348,351	-0.013 ± 0.2102	0.005 ± 0.2138
TG: Week 10, n=376,393	-0.039 ± 1.3563	-0.065 ± 0.8045
TG: Week 26, n=348,351	0.025 ± 1.1949	-0.028 ± 0.9342

Notes
[97] - Safety Population.
[98] - Safety Population.

No statistical analyses for this end point

Secondary: Number of participants with vital signs of clinical concern

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End point title

Number of participants with vital signs of clinical concern

End point description

Vital signs included systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate values. Assessment of vitals were performed with the participant in a semi recumbent or seated position having rested in this position for at least 5 minutes before each reading. The potential clinical concern values were: SBP: <100 millimeters of mercury (mmHg) and >170 mmHg, DBP: <50 mmHg and >110 mmHg and pulse rate: <50 beats per minute (bpm) and > 120 bpm. Number of participants with vital signs of clinical concern are presented.

End point type

Secondary

End point timeframe

Up to 30 weeks

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	397 ^[99]	411 ^[100]
Units: Participants
SBP: < 100 mmHg	21	20
SBP: > 170 mmHg	27	30
DBP: < 50 mmHg	1	4
DBP: > 110 mmHg	1	5
Pulse Rate: < 50 bpm	4	9
Pulse Rate: > 120 bpm	3	1

Notes
[99] - Safety Population. Only those participants available at the specified time points were analyzed.
[100] - Safety Population. Only those participants available at the specified time points were analyzed.

No statistical analyses for this end point

Secondary: Number of participants with clinically significant change in electrocardiogram (ECG) parameters

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End point title

Number of participants with clinically significant change in electrocardiogram (ECG) parameters

End point description

A single 12-lead ECG recordings were performed in a participant in semi recumbent position for 10 to 15 minutes before obtaining the ECG. Any clinically significant favorable and unfavorable findings are reported.

End point type

Secondary

End point timeframe

Up to 30 weeks

End point values	Albiglutide + Insulin Glargine	Insulin Lispro + Insulin Glargine
Number of subjects analysed	384 ^[101]	394 ^[102]
Units: Participants
Clinically Significant Change: Favorable	18	9
Clinically Significant Change: Unfavorable	4	5

Notes
[101] - Safety Population. Only those participants available at the specified time points were analyzed.
[102] - Safety Population. Only those participants available at the specified time points were analyzed.

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Up to 26 weeks

Adverse event reporting additional description

On-therapy SAE and non-serious AE were collected for Safety Population which comprised of all participants who receive at least 1 dose of randomized study medication.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

20.1

Reporting group title

Insulin Lispro + Insulin Glargine

Reporting group description

During standardization period, participants transitioned from basal bolus regimen received during screening period to insulin glargine plus insulin lispro. Eligible participants continued with the same doses as at the end of the standardization period and doses were adjusted according to protocol-defined insulin titration algorithms. Participants received Insulin Glargine along with Insulin Lispro during the treatment period.

Reporting group title

Albiglutide + Insulin Glargine

Reporting group description

During standardization period, participants transitioned from basal bolus regimen received during screening period to insulin glargine plus insulin lispro. Eligible participants received Albiglutide 30 mg weekly SC injection during the treatment period and insulin lispro dose was down-titrated to half that used in the standardization period. At Week 4, Albiglutide was up-titrated to 50 mg weekly SC injection and insulin lispro was stopped for the remainder of the treatment period.

Serious adverse events	Insulin Lispro + Insulin Glargine	Albiglutide + Insulin Glargine
Total subjects affected by serious adverse events
subjects affected / exposed	31 / 413 (7.51%)	23 / 400 (5.75%)
number of deaths (all causes)	1	0
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon
subjects affected / exposed	1 / 413 (0.24%)	0 / 400 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Breast cancer
subjects affected / exposed	1 / 413 (0.24%)	0 / 400 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Teratoma
subjects affected / exposed	0 / 413 (0.00%)	1 / 400 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
Peripheral ischaemia
subjects affected / exposed	1 / 413 (0.24%)	1 / 400 (0.25%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypertensive crisis
subjects affected / exposed	1 / 413 (0.24%)	0 / 400 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral arterial occlusive disease
subjects affected / exposed	0 / 413 (0.00%)	1 / 400 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral artery stenosis
subjects affected / exposed	1 / 413 (0.24%)	0 / 400 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral vascular disorder
subjects affected / exposed	0 / 413 (0.00%)	1 / 400 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	0 / 413 (0.00%)	1 / 400 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Non-cardiac chest pain
subjects affected / exposed	1 / 413 (0.24%)	0 / 400 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Reproductive system and breast disorders
Metrorrhagia
subjects affected / exposed	1 / 413 (0.24%)	0 / 400 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Uterine polyp
subjects affected / exposed	0 / 413 (0.00%)	1 / 400 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
subjects affected / exposed	0 / 413 (0.00%)	1 / 400 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Ligament injury
subjects affected / exposed	1 / 413 (0.24%)	0 / 400 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Multiple injuries
subjects affected / exposed	0 / 413 (0.00%)	1 / 400 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Perineal injury
subjects affected / exposed	1 / 413 (0.24%)	0 / 400 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Thoracic vertebral fracture
subjects affected / exposed	0 / 413 (0.00%)	1 / 400 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	2 / 413 (0.48%)	1 / 400 (0.25%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Angina unstable
subjects affected / exposed	1 / 413 (0.24%)	1 / 400 (0.25%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Angina pectoris
subjects affected / exposed	1 / 413 (0.24%)	0 / 400 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	1 / 413 (0.24%)	0 / 400 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Atrial flutter
subjects affected / exposed	0 / 413 (0.00%)	1 / 400 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Atrioventricular block complete
subjects affected / exposed	0 / 413 (0.00%)	1 / 400 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac failure congestive
subjects affected / exposed	1 / 413 (0.24%)	0 / 400 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Nervous system disorders
Syncope
subjects affected / exposed	1 / 413 (0.24%)	1 / 400 (0.25%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Brain stem infarction
subjects affected / exposed	1 / 413 (0.24%)	0 / 400 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Carpal tunnel syndrome
subjects affected / exposed	1 / 413 (0.24%)	0 / 400 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cerebrovascular accident
subjects affected / exposed	1 / 413 (0.24%)	0 / 400 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Facial paralysis
subjects affected / exposed	0 / 413 (0.00%)	1 / 400 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hyperaesthesia
subjects affected / exposed	0 / 413 (0.00%)	1 / 400 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ischaemic stroke
subjects affected / exposed	1 / 413 (0.24%)	0 / 400 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Sciatica
subjects affected / exposed	0 / 413 (0.00%)	1 / 400 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	1 / 413 (0.24%)	0 / 400 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ear and labyrinth disorders
Conductive deafness
subjects affected / exposed	0 / 413 (0.00%)	1 / 400 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vertigo positional
subjects affected / exposed	0 / 413 (0.00%)	1 / 400 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Eye disorders
Angle closure glaucoma
subjects affected / exposed	0 / 413 (0.00%)	1 / 400 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Colitis
subjects affected / exposed	1 / 413 (0.24%)	0 / 400 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Mesenteric artery stenosis
subjects affected / exposed	0 / 413 (0.00%)	1 / 400 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	0 / 413 (0.00%)	1 / 400 (0.25%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Rectal haemorrhage
subjects affected / exposed	1 / 413 (0.24%)	0 / 400 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis acute
subjects affected / exposed	1 / 413 (0.24%)	0 / 400 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 413 (0.00%)	1 / 400 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Pneumonia
subjects affected / exposed	2 / 413 (0.48%)	1 / 400 (0.25%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Osteomyelitis
subjects affected / exposed	2 / 413 (0.48%)	0 / 400 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	0 / 413 (0.00%)	1 / 400 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 413 (0.00%)	1 / 400 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Influenza
subjects affected / exposed	0 / 413 (0.00%)	1 / 400 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	0 / 413 (0.00%)	1 / 400 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Hypoglycaemia
subjects affected / exposed	6 / 413 (1.45%)	0 / 400 (0.00%)
occurrences causally related to treatment / all	6 / 6	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Diabetes mellitus
subjects affected / exposed	1 / 413 (0.24%)	0 / 400 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Insulin Lispro + Insulin Glargine	Albiglutide + Insulin Glargine
Total subjects affected by non serious adverse events
subjects affected / exposed	101 / 413 (24.46%)	114 / 400 (28.50%)
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	18 / 413 (4.36%)	31 / 400 (7.75%)
occurrences all number	19	51
Nausea
subjects affected / exposed	7 / 413 (1.69%)	37 / 400 (9.25%)
occurrences all number	7	53
Infections and infestations
Influenza
subjects affected / exposed	36 / 413 (8.72%)	24 / 400 (6.00%)
occurrences all number	42	30
Viral upper respiratory tract infection
subjects affected / exposed	34 / 413 (8.23%)	25 / 400 (6.25%)
occurrences all number	39	33
Urinary tract infection
subjects affected / exposed	23 / 413 (5.57%)	22 / 400 (5.50%)
occurrences all number	24	25

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

01 Jun 2015

Amendment No. 1: Clarify potentially confusing text. Add details of sensitivity analyses that will assess the impact of missing data for the noninferiority test. Introduce additional flexibility into glycemic eligibility criteria at Screening and to the process for transitioning participants from their prior basal-bolus insulin therapy to insulin glargine and insulin lispro at the beginning of the Standardization Period, as well as provide additional flexibility to the investigator when adjusting insulin glargine and insulin lispro. Further mitigate the potential risk of hypoglycemia, as well as enhance participants education and training pertaining to hypoglycemic events. Add an optional fasting glycosylated hemoglobin (HbA1c) test at Screening to aid investigators in the selection of participants who may be good candidates for the study. Add a stimulated C-peptide assessment at Screening as a complimentary assessment for participants to demonstrate reserve insulin secretory capacity. Incorporate other administrative changes.

10 Jun 2015

Amendment No. 2: The inclusion criterion pertaining to adequate contraception was updated to indicate that progestogen-only pills are only acceptable if they have a Pearl Index of less than 1.0. A criterion was added to exclude persons who have been put in an institution because of official or legal order. A criterion was added to exclude employees (or the employee’s relatives) of the sponsor, the contract research organization, or the investigative site.

24 Sep 2015

Amendment No. 3: Correct International System of units (SI units) for select blood glucose concentrations millimole per liter (mmol/L) for insulin titration. Combine global amendment 01 and country-specific amendments into a single protocol document. To aid clarity, country-specific requirements have been clearly identified. Incorporate other administrative changes.

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.

None reported

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Clinical trials

Clinical Trial Results: Albiglutide + Insulin Glargine Versus Insulin Lispro + Insulin Glargine in the Treatment of Subjects With Type 2 Diabetes Mellitus: The Switch Study

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from Baseline in glycosylated hemoglobin (HbA1c) at Week 26

Primary: Change from Baseline in glycosylated hemoglobin (HbA1c) at Week 26

Secondary: Number of participants treated with once-weekly albiglutide that were able to discontinue insulin lispro at Week 4 and did not meet prespecified criteria for severe, persistent hyperglycemia through Week 26

Secondary: Number of participants treated with once-weekly albiglutide that were able to discontinue insulin lispro at Week 4 and did not meet prespecified criteria for severe, persistent hyperglycemia through Week 26

Secondary: Percentage of participants with severe or documented symptomatic hypoglycemia through Week 26

Secondary: Percentage of participants with severe or documented symptomatic hypoglycemia through Week 26

Secondary: Change from Baseline in body weight at Week 26

Secondary: Change from Baseline in body weight at Week 26

Secondary: Change from Baseline to Week 26 in body weight

Secondary: Change from Baseline to Week 26 in body weight

Secondary: Total daily insulin dose at Week 26

Secondary: Total daily insulin dose at Week 26

Secondary: Change from Baseline to Week 26 in HbA1c

Secondary: Change from Baseline to Week 26 in HbA1c

Secondary: Change from Baseline in Fasting plasma glucose (FPG) at Week 26

Secondary: Change from Baseline in Fasting plasma glucose (FPG) at Week 26

Secondary: Change from Baseline to Week 26 in FPG

Secondary: Change from Baseline to Week 26 in FPG

Secondary: Number of participants achieving HbA1c <7.0% at Week 26

Secondary: Number of participants achieving HbA1c <7.0% at Week 26

Secondary: Number of participants achieving HbA1c <7.0% up to Week 26

Secondary: Number of participants achieving HbA1c <7.0% up to Week 26

Secondary: Number of participants achieving a HbA1c <6.5% at Week 26

Secondary: Number of participants achieving a HbA1c <6.5% at Week 26

Secondary: Number of participants achieving a HbA1c <6.5% up to Week 26

Secondary: Number of participants achieving a HbA1c <6.5% up to Week 26

Secondary: Number of participants who met prespecified criteria for severe, persistent hyperglycemia at Week 26

Secondary: Number of participants who met prespecified criteria for severe, persistent hyperglycemia at Week 26

Secondary: Number of participants meeting prespecified criteria for severe, persistent hyperglycemia up to Week 26

Secondary: Number of participants meeting prespecified criteria for severe, persistent hyperglycemia up to Week 26

Secondary: Total daily insulin dose at Week 4, Week 10 and Week 18

Secondary: Total daily insulin dose at Week 4, Week 10 and Week 18

Secondary: Total daily basal insulin (insulin glargine) at Week 4, 10, 18, and 26 visits

Secondary: Total daily basal insulin (insulin glargine) at Week 4, 10, 18, and 26 visits

Secondary: Total daily bolus insulin (insulin lispro) at Week 4, 10, 18, and 26 visits

Secondary: Total daily bolus insulin (insulin lispro) at Week 4, 10, 18, and 26 visits

Secondary: Total number of weekly insulin injections to achieve glycemic control at Baseline/Randomization and Week 4, 10, 18, and 26

Secondary: Total number of weekly insulin injections to achieve glycemic control at Baseline/Randomization and Week 4, 10, 18, and 26

Secondary: Percentage of participants achieving HbA1c <7.0% without weight gain at Week 26

Secondary: Percentage of participants achieving HbA1c <7.0% without weight gain at Week 26

Secondary: Percentage of participants achieving HbA1c <7.0% without severe or documented symptomatic hypoglycemia at Week 26

Secondary: Percentage of participants achieving HbA1c <7.0% without severe or documented symptomatic hypoglycemia at Week 26

Secondary: Percentage of participants achieving HbA1c <7.0% without weight gain and without severe or documented hypoglycemia at Week 26

Secondary: Percentage of participants achieving HbA1c <7.0% without weight gain and without severe or documented hypoglycemia at Week 26

Secondary: Number of participants with on-therapy adverse events (AE) and serious AE (SAE), and AE leading to discontinuation of randomized study medication

Secondary: Number of participants with on-therapy adverse events (AE) and serious AE (SAE), and AE leading to discontinuation of randomized study medication

Secondary: Number of participants with other AE of special interest

Secondary: Number of participants with other AE of special interest

Secondary: Percentage of participants with events of hypoglycemia with confirmed home blood glucose monitoring and/or third-party intervention through Week 26

Secondary: Percentage of participants with events of hypoglycemia with confirmed home blood glucose monitoring and/or third-party intervention through Week 26

Secondary: Number of participants with hypoglycemic events (in total and by each category as defined by the American Diabetes Association criteria)

Secondary: Number of participants with hypoglycemic events (in total and by each category as defined by the American Diabetes Association criteria)

Secondary: Number of participants with daytime and nocturnal hypoglycemia

Secondary: Number of participants with daytime and nocturnal hypoglycemia

Secondary: Number of participants with hypoglycemia with blood glucose <56 milligrams per deciliter (mg/dL) (<3.1 millimoles per liter [mmol/L]), regardless of symptoms

Secondary: Number of participants with hypoglycemia with blood glucose <56 milligrams per deciliter (mg/dL) (<3.1 millimoles per liter [mmol/L]), regardless of symptoms

Secondary: Number of participants with hematology values of clinical concern

Secondary: Number of participants with hematology values of clinical concern

Secondary: Number of participants with clinical chemistry values of clinical concern

Secondary: Number of participants with clinical chemistry values of clinical concern

Secondary: Mean urine albumin/creatinine ratio at Week 0 and Week 26

Secondary: Mean urine albumin/creatinine ratio at Week 0 and Week 26

Secondary: Mean albumin at Week 0 and Week 26

Secondary: Mean albumin at Week 0 and Week 26

Secondary: Mean creatinine at Week 0 and Week 26

Secondary: Mean creatinine at Week 0 and Week 26

Secondary: Mean specific gravity at Week 0 and Week 26

Secondary: Mean specific gravity at Week 0 and Week 26

Secondary: Number of participants with different values of potential of hydrogen (pH) at Week 0 and Week 26

Secondary: Number of participants with different values of potential of hydrogen (pH) at Week 0 and Week 26

Clinical Trial Results:
Albiglutide + Insulin Glargine Versus Insulin Lispro + Insulin Glargine in the Treatment of Subjects With Type 2 Diabetes Mellitus: The Switch Study