CompletedNCT04965935INFINITI2019Updated Jun 8, 2026Results posted

Efficacy, Mechanisms and Safety of SGLT2 Inhibitors in Kidney Transplant Recipients

A Phase 3 interventional study of Dapagliflozin 10 MG Oral Tablet and Placebo Matching Dapagliflozin Oral Tablet in Kidney Transplant Recipients, Post-transplant Diabetes Mellitus and Type 2 Diabetes, sponsored by University Health Network, Toronto. Completed at 1 site in Canada. Open to participants aged 19 Years and older. Per ClinicalTrials.gov, last updated 2026-06-08.

Sponsored by University Health Network, Toronto · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 52
Allocation: Randomized
Ages: 19 Years and older
Sex: All

Study summary

This study will be a randomized, double-blind, placebo-controlled clinical trial comparing the SGLT2 inhibitor dapagliflozin to placebo in 52 kidney transplant recipients (KTR) with or without pre-existing type 2 diabetes (T2D) or post-transplant diabetes mellitus (PTDM). The primary outcome of the trial is to determine if dapagliflozin is superior to placebo in reduction of blood pressure in KTR.

Read the detailed description

Kidney transplantation is the renal replacement therapy of choice for patients with end stage renal disease (ESRD). It has been well established that kidney transplantation improves patient survival and quality of life, and results in significant savings to the health care system.

Despite the survival benefit conferred by transplantation, KTR still face a number of challenges, especially in patients with diabetes. First, KTR still have a higher risk of mortality than their age-matched counterparts without kidney disease. This mortality risk is even greater amongst KTR with diabetes. Furthermore, mortality from cardiovascular disease (CVD) continues to be an important problem after transplantation. Another major challenge faced by KTR is the continuing risk of developing graft failure over time. Unfortunately, in the subgroup of KTR with diabetes, the incidence of graft failure is 50% higher than the general kidney transplant recipient population, and recurrent diabetic kidney disease (DKD) occurs in almost half of allografts after transplantation. Current strategies in the management of graft dysfunction and chronic kidney disease (CKD) are focused on optimizing immunosuppression and control of hypertension and dyslipidemia. Accordingly, there is an important unmet need for cardio- and renoprotective strategies to address premature death and graft loss in the KTR population.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are glucose lowering agents that are effective in the treatment of T2D, resulting not only in improved glycemic control, but also weight loss, blood pressure and albuminuria reduction. Several clinical trials have shown significant benefits of SGLT2i on cardiovascular and renal outcomes. Given the glucose-dependent and independent effects of SGLT2i, as well as the accumulating evidence demonstrating cardiorenal protection in non-KTR, the use of these agents in KTR is attractive - especially since traditional renin-angiotensin-aldosterone system inhibitors are not effective. Moreover, the use of SGLT2i as a cardiorenal protective therapy may be of particular value in KTR given the high burden of comorbidities such as diabetes, CVD and hypertension, as well as the ongoing challenges of premature death and graft loss in this population.

This study will be a randomized, double-blind, placebo-controlled clinical trial comparing the SGLT2 inhibitor dapagliflozin to placebo in 52 KTR with or without pre-existing T2D or PTDM. The primary outcome of the trial is to determine if dapagliflozin is superior to placebo in reduction of blood pressure in KTR. The secondary outcomes of this study include metabolic, vascular, renal and transplant-specific measures. These outcomes have been included to elucidate the potential mechanisms responsible for blood pressure lowering, and putative cardio- and renoprotective effects in KTR. Safety outcomes will also be assessed.

Conditions studied

Kidney Transplant Recipients
Post-transplant Diabetes Mellitus
Type 2 Diabetes

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Diabetes Mellitus, Type 2 9,359

In context

Diabetes Mellitus, Type 2

9,359 studies on the registry are indexed under Diabetes Mellitus, Type 2; 1,318 are open to participants now.

This study's enrollment of 52 is below the median of 80 across 7,525 interventional studies indexed under Diabetes Mellitus, Type 2.

Browse Diabetes Mellitus, Type 2 studies →

Lead sponsor

University Health Network, Toronto is the lead sponsor of 1,411 studies on the registry; 292 are open to participants now.

Of its 17 completed or terminated interventional studies of FDA-regulated products, 3 (18%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 19 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Male or females >18 years old ≥ 6months after kidney transplantation;
In patients with T2D or PTDM, HbA1c \<12.0%;
eGFR ≥30 ml/min/1.73m\^2 (as per the CKD-EPI equation);
BMI ≤45kg/m\^2;
Blood pressure ≤160/90 and ≥90/60 at screening.

Exclusion criteria

Exclusion Criteria:

Diagnosis of type 1 diabetes;
Presence of severe peripheral vascular disease (i.e. prior amputation, gangrene, non-healing ulcer or ischemic rest pain);
Presence of acute coronary syndrome, stroke or transient ischemic attack in the 3 months prior to screening;
Prior episode of graft pyelonephritis in the 1 month prior to screening;
Episode of acute graft rejection in the 3 months prior to screening;
Initiation of a new immunosuppressive agent or discontinuation of an immunosuppressive agent in the 1 month prior to screening;
Untreated urinary or genital tract infection;
Severe hypoglycemia within 3 months of screening, or hypoglycemia unawareness;
Pre-menopausal women who are nursing, pregnant, or of child-bearing potential and not practicing an acceptable method of birth control;
Participation in another trial with an investigational drug within 30 days of informed consent;
Alcohol or drug abuse within 3 months prior to informed consent that would interfere with trial participation;
Any ongoing clinical condition that would jeopardize subject safety or study compliance based on investigator judgement.
Patients currently using antipsychotic medications.
Use of SGLT2 inhibitors within 1 month of starting the study.

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Triple (Participant, Investigator, Outcomes assessor)
Enrollment: 52 participants (actual)

Study arms

Experimental
Dapagliflozin Tablets
Patients will be randomized to therapy with dapagliflozin 10mg PO daily for 12 weeks.
Drug: Dapagliflozin 10 MG Oral Tablet
Placebo comparator
Placebo Matching Dapagliflozin Tablets
Patients will be randomized to therapy with placebo matching dapagliflozin tablets PO daily for 12 weeks.
Drug: Placebo Matching Dapagliflozin Oral Tablet

Interventions

DrugDapagliflozin 10 MG Oral Tablet
Dapagliflozin will be administered in a dose of 10 mg/day for 12 weeks.
DrugPlacebo Matching Dapagliflozin Oral Tablet
Placebo will be administered for 12 weeks.

What researchers measure

Primary outcomes

Systolic Blood Pressure (SBP)
SBP
Time frame: Change from baseline SBP at 12 weeks of treatment

Secondary outcomes

Fasting Plasma Glucose
Fasting plasma glucose
Time frame: Change from baseline fasting plasma glucose at 12 weeks of treatment
Glycated Hemoglobin (HbA1c)
HbA1c
Time frame: Change from baseline HbA1c at 12 weeks of treatment
Carotid-femoral Pulse Wave Velocity
Measured using a Sphygmocor device
Time frame: Change from baseline arterial stiffness at 12 weeks of treatment
Systemic Vascular Resistance
Measured using non-invasive cardiac output monitor (NICOM)
Time frame: Change from baseline systemic vascular resistance at 12 weeks of treatment
Measured GFR
GFR
Time frame: Change from baseline GFR (based on plasma iohexol clearance) at 12 weeks of treatment
Proximal Tubular Natriuresis
Measured by fractional excretion of exogenous lithium (FELi)
Time frame: Change from baseline proximal tubular natriuresis at 12 weeks of treatment
UACR
Albuminuria
Time frame: Change from baseline albuminuria at 12 weeks of treatment
Weight
Weight
Time frame: Change from baseline weight at 12 weeks of treatment

Results

Posted Jun 8, 2026

Participant flow

Participant flow — Overall Study
Milestone	Dapagliflozin Tablets	Placebo Matching Dapagliflozin Tablets
Started	26	26
Completed	26	25
Not completed	0	1
Withdrew: Adverse event	0	1

Outcome measures

PrimarySystolic Blood Pressure (SBP)

SBP

Time frame:: Change from baseline SBP at 12 weeks of treatment
Reported as:: Mean · mmHg

Systolic Blood Pressure (SBP)
mmHg	Dapagliflozin Tablets	Placebo Matching Dapagliflozin Tablets
Systolic Blood Pressure (SBP)	-6.615 ± 2.084	-3.706 ± 2.12

SecondaryFasting Plasma Glucose

Fasting plasma glucose

Time frame:: Change from baseline fasting plasma glucose at 12 weeks of treatment
Reported as:: Mean · mmol/l

Fasting Plasma Glucose
mmol/l	Dapagliflozin Tablets	Placebo Matching Dapagliflozin Tablets
Fasting Plasma Glucose	0.146 ± 0.341	0.576 ± 0.346

SecondaryGlycated Hemoglobin (HbA1c)

HbA1c

Time frame:: Change from baseline HbA1c at 12 weeks of treatment
Reported as:: Mean · % of glycated hemoglobin

Glycated Hemoglobin (HbA1c)
% of glycated hemoglobin	Dapagliflozin Tablets	Placebo Matching Dapagliflozin Tablets
Glycated Hemoglobin (HbA1c)	-0.112 ± 0.115	-0.143 ± 0.117

SecondaryCarotid-femoral Pulse Wave Velocity

Measured using a Sphygmocor device

Time frame:: Change from baseline arterial stiffness at 12 weeks of treatment
Reported as:: Mean · m/s

Carotid-femoral Pulse Wave Velocity
m/s	Dapagliflozin Tablets	Placebo Matching Dapagliflozin Tablets
Carotid-femoral Pulse Wave Velocity	-0.046 ± 0.527	-0.72 ± 0.536

SecondarySystemic Vascular Resistance

Measured using non-invasive cardiac output monitor (NICOM)

Time frame:: Change from baseline systemic vascular resistance at 12 weeks of treatment
Reported as:: Mean · dynes*sec/cm^5

Systemic Vascular Resistance
dynes*sec/cm^5	Dapagliflozin Tablets	Placebo Matching Dapagliflozin Tablets
Systemic Vascular Resistance	-76.577 ± 83.311	2.106 ± 86.131

SecondaryMeasured GFR

GFR

Time frame:: Change from baseline GFR (based on plasma iohexol clearance) at 12 weeks of treatment
Reported as:: Mean · mL/min/1.73 m^2

Measured GFR
mL/min/1.73 m^2	Dapagliflozin Tablets	Placebo Matching Dapagliflozin Tablets
Measured GFR	-3.116 ± 0.99	0.37 ± 1.01

SecondaryProximal Tubular Natriuresis

Measured by fractional excretion of exogenous lithium (FELi)

Time frame:: Change from baseline proximal tubular natriuresis at 12 weeks of treatment
Reported as:: Mean · % of lithium excretion

Proximal Tubular Natriuresis
% of lithium excretion	Dapagliflozin Tablets	Placebo Matching Dapagliflozin Tablets
Proximal Tubular Natriuresis	5.229 ± 2.895	1.662 ± 2.895

SecondaryUACR

Albuminuria

Time frame:: Change from baseline albuminuria at 12 weeks of treatment
Reported as:: Mean · mg/mmol

UACR
mg/mmol	Dapagliflozin Tablets	Placebo Matching Dapagliflozin Tablets
UACR	-3.25 ± 4.394	-3.134 ± 4.473

SecondaryWeight

Weight

Time frame:: Change from baseline weight at 12 weeks of treatment
Reported as:: Mean · kg

Weight
kg	Dapagliflozin Tablets	Placebo Matching Dapagliflozin Tablets
Weight	-1.208 ± 0.421	0.706 ± 0.429

Adverse events

Collected over 12 weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Dapagliflozin Tablets	0/26 (0%)	0/26 (0%)	2/26 (7.7%)
Placebo Matching Dapagliflozin Tablets	0/26 (0%)	1/26 (3.8%)	2/26 (7.7%)

Most frequent serious events

Most frequent serious events
Event	Dapagliflozin Tablets	Placebo Matching Dapagliflozin Tablets
Lupus flareImmune system disorders	0/26	1/26

Most frequent other events

Most frequent other events
Event	Dapagliflozin Tablets	Placebo Matching Dapagliflozin Tablets
Mild hypoglycaemic episodesEndocrine disorders	2/26	2/26

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Dapagliflozin Tablets	Placebo Matching Dapagliflozin Tablets	Total
Median	57 (46.8 to 61.8)	54 (48.5 to 60)	56 (48 to 60.2)

Sex: Female, Male
Sex: Female, Male(Participants)	Dapagliflozin Tablets	Placebo Matching Dapagliflozin Tablets	Total
Female	4	7	11
Male	22	19	41

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Dapagliflozin Tablets	Placebo Matching Dapagliflozin Tablets	Total
Asian	10	8	18
Black	1	5	6
Caucasian	13	11	24
Latinx	0	1	1
Other	2	1	3

Time since transplant
Time since transplant(years)	Dapagliflozin Tablets	Placebo Matching Dapagliflozin Tablets	Total
Mean	9.1 ± 11.3	6.7 ± 5.9	7.9 ± 9

Estimated glomerular filtration rate (eGFR)
Estimated glomerular filtration rate (eGFR)(mL/min/1.73 m^2)	Dapagliflozin Tablets	Placebo Matching Dapagliflozin Tablets	Total
Median	62.4 (51.2 to 87.5)	64.7 (52.2 to 78.5)	64.3 (50.8 to 83.2)

Urine albumin-to-creatinine ratio (UACR)
Urine albumin-to-creatinine ratio (UACR)(mg/mmol)	Dapagliflozin Tablets	Placebo Matching Dapagliflozin Tablets	Total
Median	2.5 (1.6 to 8.3)	2 (1 to 6.8)	2.3 (1.1 to 7.6)

Study locations

1 site

Renal Physiology Laboratory
Toronto, Ontario, Canada

References and documents

Publications

Sridhar VS, Kugathasan L, Lytvyn Y, Liu H, Deng Y, Lovblom LE, Nardone M, Yuen DA, Chen Y, Hua J, Aronson Y, Mohsen M, Kim SJ, Udell JA, Perkins BA, Stevens J, Touw DJ, Heerspink HJL, Cherney DZI, Singh SKS. Efficacy, Mechanisms, and Safety of Sodium-Glucose Cotransporter-2 Inhibitors in Kidney Transplant Recipients: A Randomized, Double-Blind, Placebo-Controlled Trial. Clin J Am Soc Nephrol. 2026 Apr 1;21(4):664-679. doi: 10.2215/CJN.0000000951. Epub 2025 Dec 12. PubMed 41385300 ↗

Study documents

Study protocol · Mar 18, 2022
Statistical analysis plan · Mar 7, 2025

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jun 8, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT04965935
Lead sponsor: University Health Network, Toronto
Responsible party: Sunita Singh, MD, MSc, FRCPC (Clinician Scientist, University Health Network, Toronto) — Principal investigator
First posted: Jul 16, 2021
Start date: Jul 15, 2021
Primary completion: Aug 30, 2024
Completion: Aug 30, 2024
Results posted: Jun 8, 2026
Last update: Jun 8, 2026

Study contacts

Sunita KS Singh, MD MSc FRCPC

principal investigator · University Health Network, Toronto General Hospital

Oversight

Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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