SGLT2 Inhibitor + GLP-1 Agonist for Kidney Transplant Recipients
(HALLMARK Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University Health Network, Toronto
Must not be taking: SGLT2i, GLP-1RA
Disqualifiers: Type 1 diabetes, Multi-organ transplant, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial is testing two diabetes medications, dapagliflozin and semaglutide, alone and together, in kidney transplant patients. The goal is to see if these drugs can safely protect their kidneys and hearts by lowering blood sugar and blood pressure. Dapagliflozin has shown benefits in reducing cardiovascular and kidney issues in chronic kidney disease patients, while semaglutide has demonstrated kidney-protective effects in type 2 diabetes patients.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but you cannot have used SGLT2 inhibitors or GLP-1 receptor agonists within 30 days before the trial starts.
What data supports the effectiveness of the drug combination of SGLT2 Inhibitor and GLP-1 Agonist for kidney transplant recipients?
Research shows that dapagliflozin, an SGLT2 inhibitor, is effective in reducing the risk of kidney function decline and heart-related issues in people with chronic kidney disease. Additionally, semaglutide, a GLP-1 agonist, has been shown to improve blood sugar control and reduce weight, which can benefit kidney health.
12345Is the combination of SGLT2 inhibitors and GLP-1 agonists safe for humans?
Dapagliflozin (Farxiga), an SGLT2 inhibitor, is approved for reducing kidney and heart risks in adults with chronic kidney disease, showing it is generally safe for these conditions. GLP-1 agonists like semaglutide have an excellent safety profile and provide cardiovascular and kidney benefits, making them safe for use in humans.
16789What makes the drug combination of SGLT2 inhibitor and GLP-1 agonist unique for kidney transplant recipients?
This drug combination is unique because it combines two types of medications, SGLT2 inhibitors and GLP-1 agonists, which have shown kidney-protective effects in other conditions like type 2 diabetes. This approach is novel for kidney transplant recipients, as it may offer metabolic benefits and protect kidney function, which are not typically addressed by standard treatments for this group.
310111213Eligibility Criteria
This trial is for kidney transplant recipients aged 18 or older, with a BMI of 18.5-40 and stable blood pressure. They must be at least 3 months post-transplantation with decent kidney function (eGFR ≥20). Diabetics can join if their HbA1c is below 12%. Exclusions include recent use of similar drugs, risk of dehydration or electrolyte issues, severe infections, uncontrolled hypertension, hypersensitivity to the drugs tested, pregnancy, certain cancers or genetic conditions.Inclusion Criteria
Estimated glomerular filtration rate (eGFR) equal to or greater than 20 ml/min/1.73m2
Body-mass index (BMI) between 18.5 and 40 kg/m2
I am over 18 and had a kidney transplant more than 3 months ago.
+3 more
Exclusion Criteria
Any other clinical condition that, based on Investigator's judgment, would jeopardize patient safety during trial participation or would affect the study outcome (e.g. immunocompromised patients, active malignancy, patients who might be at higher risk of developing genital or mycotic infections, patients with chronic viral infections, uncontrolled hypertension, cardiorenal and/or hepatorenal syndrome)
I am currently being treated for BK, CMV, or EBV infection.
I have had an amputation or experience pain at rest due to poor blood flow.
+15 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Monotherapy Treatment
Participants receive either semaglutide or dapagliflozin for 12 weeks
12 weeks
Weekly visits for semaglutide, daily monitoring for dapagliflozin
Combination Therapy Treatment
Participants receive a combination of semaglutide and dapagliflozin for 12 weeks
12 weeks
Weekly visits for combination therapy
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests the combination therapy using Dapagliflozin and Semaglutide over a period of 12 weeks in kidney transplant recipients (KTR), both with and without type 2 diabetes (T2D). It aims to assess how effective this treatment is short-term and what safety concerns might arise.
2Treatment groups
Experimental Treatment
Group I: SemaglutideExperimental Treatment2 Interventions
Semaglutide Subcutaneous 0.25mg once weekly for 4 weeks, then 0.5mg once weekly for 4 weeks, then 1mg once weekly for 4 weeks.
Group II: DapagliflozinExperimental Treatment2 Interventions
Dapagliflozin Tablets Total Dose 10mg daily for 12 weeks
Dapagliflozin is already approved in European Union, United States, Canada for the following indications:
🇪🇺 Approved in European Union as Forxiga for:
- Type 2 diabetes
- Heart failure
- Chronic kidney disease
🇺🇸 Approved in United States as Farxiga for:
- Type 2 diabetes
- Heart failure
- Chronic kidney disease
🇨🇦 Approved in Canada as Farxiga for:
- Type 2 diabetes
- Heart failure
- Chronic kidney disease
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Toronto General HospitalToronto, Canada
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Who Is Running the Clinical Trial?
University Health Network, TorontoLead Sponsor
References
Antidiabetic Drug Approved to Reduce Risk of Kidney Disease. [2023]Dapagliflozin (Farxiga) is now approved to reduce the risk of declining kidney function, kidney failure, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease with or without type 2 diabetes.
Exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy (DURATION-8): a 28 week, multicentre, double-blind, phase 3, randomised controlled trial. [2022]Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce glycaemia and weight, and improve cardiovascular risk factors via different mechanisms. We aimed to compare the efficacy and safety of co-initiation of the GLP-1 receptor agonist exenatide and the SGLT2 inhibitor dapagliflozin with exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled by metformin.
Review of Newer Antidiabetic Agents for Diabetes Management in Kidney Transplant Recipients. [2021]This systematic review describes the efficacy, safety, and drug interactions of dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium-glucose transport protein 2 (SGLT2) inhibitors in kidney transplant recipients (KTRs).
Efficacy and Safety of Semaglutide, a Glucagon-Like Peptide-1 Receptor Agonist in Real-Life: A Case Series of Patients in Maintenance Incremental Hemodialysis. [2022]The glucagon-like peptide-1 receptor agonists (GLP-1RA) are among the newest treatment options available for managing of type 2 diabetes mellitus and slowing the progression of diabetes kidney disease (DKD). Subcutaneous (SC) semaglutide (Ozempic®) is a GLP-1RA with an extended half-life of approximately 1 week. GLP-1RA are highly effective in improving glycemic control and also show other beneficial effects such as increased natriuresis; decreased blood pressure and albuminuria; reduction of oxidative stress and inflammation; delay of gastric emptying and suppress appetite; the latter may result in significant weight loss. GLP-1RA can be used in patients with advanced-stage CKD; the European Medicines Agency has approved the use of all commercially available human GLP-1 analogs up to a minimal eGFR of 15 mL/min/1.73 m2. However, studies of safety and use of these agents in renal replacement therapy are scarce. Therefore, herein we present 3 cases of patients with advanced DKD in maintenance incremental hemodialysis with 1 session per week to describe the efficacy and safety of the SC semaglutide treatment and the favorable effects on glycemic control, lowering HbA1c, albuminuria, weight, blood pressure control, and preservation of residual kidney function (RKF) during a 6-month follow-up in a hospital hemodialysis unit in Spain. These effects could produce an improvement in morbidity and mortality and could also prevent albuminuria and preserve the RKF. This may allow our patients to maintain a weekly hemodialysis session and could facilitate their inclusion in the kidney transplant waiting lists.
Comparison of efficacy and safety of three novel hypoglycemic agents in patients with severe diabetic kidney disease: A systematic review and network meta-analysis of randomized controlled trials. [2022]To analyze the efficacy and safety of three novel hypoglycemic agents, glucagon-like peptidyl-1 receptor agonists, dipeptidyl peptidase-4 inhibitors (DPP-4i), and sodium-glucose cotransporter two inhibitors (SGLT2i) in type 2 diabetes mellitus (T2DM) patients with severe chronic kidney disease (CKD) (defined in this study as CKD stage 3 B or above, eGFR< 45 mL/min/1.73 m²) based on important RCTs to date.
Dapagliflozin no longer licensed for type 1 diabetes. [2022]Overview of: Medicines and Healthcare products Regulatory Agency. Dapagliflozin (Forxiga): no longer authorised for treatment of type 1 diabetes mellitus. Drug Safety Update 2021;15:3.
Dapagliflozin: A Sodium Glucose Cotransporter 2 Inhibitor for the Treatment of Diabetes Mellitus. [2021]To review clinical evidence for the efficacy, safety, and tolerability of dapagliflozin (Farxiga-AstraZeneca), a sodium glucose cotransporter 2 inhibitor, as monotherapy or in combination with other hypoglycemic agents for the treatment of type 2 diabetes.
Pharmacokinetics, pharmacodynamics and clinical efficacy of dapagliflozin for the treatment of type 2 diabetes. [2021]Dapagliflozin (DAPA) (Farxiga or Forxiga) is a sodium glucose cotransporter 2 (SGLT2) inhibitor approved for type 2 diabetes mellitus(T2DM) treatment.
Glucagon-like peptide 1(GLP-1) receptor agonists in the management of the patient with type 2diabetes mellitus and chronic kidney disease: an approach for the nephrologist. [2023]Diabetic kidney disease, a common complication in patients with type 2 diabetes mellitus, is associated with a markedly increased morbidity and mortality, especially of cardiovascular origin, and faster progression to end-stage renal disease. To date, reducing cardiovascular and renal risk in this population was based on strict control of cardiovascular risk factors and the renin-angiotensin system blockade. More recently, sodium-glucose cotransporter type 2 inhibitors have demonstrated to offer cardiovascular and renal protection, but the residual risk remains high and their antihyperglycemic efficacy is limited in moderate-severe CKD. Therefore, drugs with a potent antihyperglycemic effect, independent of the glomerular filtration rate, with a low risk of hypoglycemia, that reduce weight in overweight/obese patients and that provide cardiovascular and renal protection, such as GLP-1 receptor agonists, are needed. However, these drugs require subcutaneous administration, which may limit their early use. The recent availability of oral semaglutide may facilitate the early introduction of this family with proven cardiovascular and renal benefits and excellent safety profile. In this review the family is analyzed as well as their cardiovascular and renal effects.
Parameters influencing renal response to SGLT2 inhibitors and GLP1 receptor agonists in type 2 diabetes patients with preserved renal function: a comparative, prospective study. [2023]SGLT2 inhibitors (SGLT2i) and GLP1 receptor agonists (GLP1-RA) protect the kidney in type 2 diabetes (T2DM) subjects. The role of patient's phenotype years before starting the treatment in determining the kidney response to these drugs has never been evaluated.
Glucagon-like peptide 1 receptor agonists in end-staged kidney disease and kidney transplantation: A narrative review. [2023]Glucagon-like peptide 1 receptor agonists (GLP-1RA) improve glycemic control and promote weight loss in type 2 diabetes (DM2) and obesity. We identified studies describing the metabolic benefits of GLP-1RA in end-staged kidney disease (ESKD) and kidney transplantation.
Separate and combined effects of semaglutide and empagliflozin on kidney oxygenation and perfusion in people with type 2 diabetes: a randomised trial. [2023]Glucagon-like peptide-1 receptor agonists (GLP-1ras) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) have shown kidney-protective effects. Improved kidney oxygenation and haemodynamic changes are suggested mechanisms; however, human data are scarce. We therefore investigated whether semaglutide (GLP-1ra), empagliflozin (SGLT2i) or their combination improve kidney oxygenation and perfusion.
Effect of glucagon-like peptide 1 receptor agonists on the renal protection in patients with type 2 diabetes: A systematic review and meta-analysis. [2022]Glucagon-like peptide 1(GLP-1) receptor agonists are used in patients with type 2 diabetes as hypoglycemic drugs; a growing body of evidence has clarified their renoprotective benefits. We performed a meta-analysis to summarize the most recent evidence on the renal benefits of GLP-1 receptor agonists from clinical trials of patients with type 2 diabetes.