Clinical Trial Results:
A study to investigate the potential renoprotective role of sodium-glucose transporter-2 (SGLT-2) antagonist Dapagliflozin in Type 2 diabetic patients with diabetic nephropathy
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Summary
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EudraCT number |
2013-004042-42 |
Trial protocol |
GB |
Global end of trial date |
08 Jul 2025
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Results information
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Results version number |
v1(current) |
This version publication date |
28 Aug 2026
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First version publication date |
28 Aug 2026
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Other versions |
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Summary report(s) |
DEER CSR FINAL 18Feb26 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
DEER
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
King's College London
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Sponsor organisation address |
The Strand, London, United Kingdom, WC2R 2LS
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Public contact |
Dr Janaka Karalliedde, King's College London, 0044 02078484464, j.karalliedde@kcl.ac.uk
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Scientific contact |
Dr Janaka Karalliedde, King's College London, 0044 02078484464, j.karalliedde@kcl.ac.uk
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Sponsor organisation name |
Guy's and St Thomas' NHS Foundation Trust
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Sponsor organisation address |
Great Maze Pond, London, United Kingdom, SE19RT
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Public contact |
Dr Janaka Karalliedde, King’s College London , 0044 02078484464, j.karalliedde@kcl.ac.uk
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Scientific contact |
Dr Janaka Karalliedde, Guy's and St Thomas' NHS Foundation Trust, 0044 02078484464, j.karalliedde@kcl.ac.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
05 Dec 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
05 Dec 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
08 Jul 2025
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To study the potential protective role of Dapagliflozin on renal disease in patients with Type 2 diabetes and diabetic renal disease. We aim to evaluate in this trial if the combination of Dapagliflozin and Ramipril (an established reno-protective drug) significantly reduces microalbuminuria ( a markers of renal damage) as compared to Ramipril alone in patients with type-2 diabetes with preserved renal function and residual albuminuria despite currently available optimal treatments.
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Protection of trial subjects |
Patients were free to withdraw from the study at any time without giving a reason. Patients were informed that if they requested to withdraw from the study, at any time during the trial, then this would have no negative consequences. The investigator could also withdraw patients from the trial if they deemed it appropriate for safety or ethical reasons or if it was considered detrimental to the well-being of the patient. Patients who withdrew or were withdrawn underwent a final evaluation at [visit]. Patients who did not complete the study through to [visit], unless removed due to toxicity,
could have been replaced.
Full documentation was made of any withdrawals that occurred during the study in the CRF. The Investigator documented the date and time of the withdrawal and results of any assessments made at this time. If the patient withdrew because of an adverse event (AE), or a serious adverse event (SAE) then details were forwarded to the Ethics committee as required. The investigator also forwarded details to King’s College University. King’s College University forwarded details to the regulatory authorities as appropriate.
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Background therapy |
Over a lifetime diabetic nephropathy occurs in approximately 30-35 per cent of type-1 and type-2 diabetic patients. These patients are at heightened risk of premature cardiovascular death and progression to end stage renal diseaseDiabetes and in particular diabetic renal disease is characterised by activation of the RAAS. Despite the development and increased use of inhibitors of the RAAS, in recent decades there remains an unmet need for novel treatments to address the growing global burden of diabetic renal disease. We hypothesise that the increase inhibition of proximal tubule sodium reabsorption and concomitant increased delivery of urinary sodium to the distal nephron induced by SGLT2 inhibitor Dapagliflozin would trigger the RAAS and, in patients treated with ACE-inhibitors or ARB, this would result in an increase in angiotensin-I and II levels. As both angiotensin-I and II are substrates for ACE-2, the combination treatment with Dapagliflozin + ACE-inhibitor (Ramipril) would result in increased ACE-2 activity and excess production of angiotensin 1-9 and 1-7 which will be beneficial as these isoforms have cardiovascular-renal protective effects. In summary Dapagliflozin treatment may provide cardio-renal benefits by potentiation of RAAS blockade with concomitant production of beneficial/protective RAAS metabolites as well reducing intraglomerular pressure that will aid/confer both renal and vascular protection. | ||
Evidence for comparator |
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Actual start date of recruitment |
01 Sep 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 33
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Worldwide total number of subjects |
33
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EEA total number of subjects |
33
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
25
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From 65 to 84 years |
8
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||||||||
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Pre-assignment
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Screening details |
- | |||||||||||||||
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Pre-assignment period milestones
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Number of subjects started |
68 [1] | |||||||||||||||
Number of subjects completed |
33 | |||||||||||||||
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Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
Not meeting inclusion criteria: 34 | |||||||||||||||
Reason: Number of subjects |
Declined to participate: 1 | |||||||||||||||
| Notes [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: we do not count screening participants as enrolled |
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||
Blinding implementation details |
Trial design is prospective randomised parallel group open label trial but all data analyses was performed blinded to group allocation and all patient data was anonymised.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Dapagliflozin + Ramipril | |||||||||||||||
Arm description |
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Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Dapagliflozin and Ramipril
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Dapagliflozin 10 mg Once daily + Ramipril 10mg Once daily
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Arm title
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Ramipril only | |||||||||||||||
Arm description |
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Arm type |
Active comparator | |||||||||||||||
Investigational medicinal product name |
Ramipril
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Ramipril 10mg Once daily
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Baseline characteristics reporting groups
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Reporting group title |
Dapagliflozin + Ramipril
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Reporting group description |
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Reporting group title |
Ramipril only
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Reporting group description |
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End points reporting groups
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Reporting group title |
Dapagliflozin + Ramipril
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Reporting group description |
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Reporting group title |
Ramipril only
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Reporting group description |
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End point title |
Albumin Excretion Rate (AER) [1] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Baseline
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: 'Please see uploaded report |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Albumin Excretion Rate (AER) [2] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
End of study
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Please see uploaded report |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Difference in Albumin Excretion Rate (AER) [3] [4] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Baseline to 24 Weeks
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Please see uploaded report [4] - 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: Please see uploaded report |
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline to end of study
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
26.1
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Reporting groups
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Reporting group title |
Dapagliflozin + Ramipril
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Reporting group description |
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Reporting group title |
Ramipril only
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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05 Jan 2016 |
SA0001: Protocol amended to reflect current practice: Inclusion criteria amended to only require one result for urine albumin creatinine ratio (ACR>3 mg/mmol) and also to allow any anti-diabetic treatment. Patients can now be included if they are on insulin. |
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21 Sep 2016 |
SA002: In light of the SmPC change exclusion criteria will be update :
Patients with a history of DKA or at high risk of DKA (T2DM patients with known low C-peptide (<0.25nmol/l), patients with a history of pancreatitis, patients with conditions that lead to restricted food intake or severe dehydration.
Other changes to PIS and Protocol
• Urine dipstick analysis (Urinalysis) will be performed at screening visit 1.
Protocol pages 10, 18 and 23
Previous wording
Urinalysis (Visits 3,5,6 and 7):
New Wording
Urinalysis (Visits 1,3,5,6 and 7):
This is will enable a more recent/up to date status of urine proteinuria/albuminuria status to be documented and to ensure a recent history of albuminuria is available and can be documented.
• Clarification that liver function tests will be checked at screening (visit 1).
Protocol pages 10, 18 and 23
Previous wording in trial flow chart.
Liver function tests (visit 3, 5 and 6):
New Wording
Liver function tests (visit 1, 3, 5 and 6):
The need for a liver function test (LFT) check at screening has been more clearly detailed in trial protocol, description of procedures and related flow chart.
Inclusion of local GP practices as patient identification centres (PIC)
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01 Dec 2018 |
SA003: Update to RSI and protocol V2 (Includes additional responses to REC queries, updating protocol to V2.1)
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26 Jun 2019 |
SA004: Extension of study/ clarification of study end
Update to Protocol V3.0 |
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29 Aug 2019 |
SA005: Notification of update RSI to MHRA |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Age group breakdown for trial participants data was not provided in the CSR so a manual calculation was made to provide this information into EudraCT however, there was 1 missing data and an inference was made that they were in the 18-64 category. | |||
