What side effects are associated with this type of intervention?

SGLT2 inhibitors like dapagliflozin can cause genital infections, urinary tract infections, dehydration, and in some cases, ketoacidosis and lower limb amputations. GLP-1 receptor agonists like semaglutide may lead to gastrointestinal issues such as nausea, vomiting, and diarrhea, and have been linked to an increased risk of pancreatitis and thyroid tumors. Both drug classes have demonstrated cardiovascular and renal benefits, which are important considerations for kidney transplant recipients.

What prior FDA approvals exist?

The FDA has approved several SGLT2 inhibitors, such as dapagliflozin, canagliflozin, and empagliflozin, for the treatment of diabetes mellitus. These drugs have shown benefits in glycemic control, weight reduction, and renal function preservation in various patient populations, including those with chronic kidney disease. Additionally, GLP-1 receptor agonists like semaglutide and liraglutide have been approved for their efficacy in enhancing insulin secretion, inhibiting glucagon release, and promoting weight loss. While specific FDA approvals for the combination therapy of dapagliflozin and semaglutide in kidney transplant recipients are not detailed, these drugs individually have demonstrated safety and efficacy in managing diabetes and preserving renal function in similar patient groups.

What other types of research exist?

Promising alternatives to dapagliflozin and semaglutide combination therapy for kidney transplant recipients in 2024 include: 1) Dipeptidyl Peptidase-4 (DPP-4) inhibitors like sitagliptin and vildagliptin, which enhance the body's incretin system to regulate glucose levels. 2) Sodium-Glucose Cotransporter-2 (SGLT2) inhibitors other than dapagliflozin, such as empagliflozin and canagliflozin, which have shown benefits in cardiovascular and renal outcomes. 3) Thiazolidinediones like pioglitazone, which improve insulin sensitivity. These alternatives offer different mechanisms of action and have been studied for their safety and efficacy in patients with diabetes and renal conditions.

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Sodium Glucose Co-Transporter-2 Inhibitor

SGLT2 Inhibitor + GLP-1 Agonist for Kidney Transplant Recipients (HALLMARK Trial)

Phase 2

Recruiting

Led By Sunita Singh, MD MSc FRCPC

Research Sponsored by University Health Network, Toronto

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects may include risks related to volume depletion like low blood pressure or imbalance in body salts; genital or urinary tract infections; possible allergic reactions; hypoglycemia especially in diabetic patients; pancreatitis; and possibly others not listed.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ]

This trial's timeline: 3 weeks for screening, Varies for treatment, and from baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ] for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Proximal tubular natriuresis with combination therapy

Proximal tubular natriuresis with monotherapy

Secondary study objectives

Arterial stiffness

Change in body composition (percent body mass, body fat, and muscle mass)

Change in concentration of urine glucose excretion

+6 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Dapagliflozin 10 MG

2019

Completed Phase 4

~310

Semaglutide, 1.0 mg/mL

2018

Completed Phase 1

~70

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Dapagliflozin, an SGLT2 inhibitor, reduces blood glucose by preventing glucose reabsorption in the kidneys, leading to increased glucose excretion in the urine. Semaglutide, a GLP-1 receptor agonist, enhances insulin secretion and inhibits glucagon release, helping to regulate blood sugar levels. These mechanisms are vital for Kidney Transplant Recipients (KTRs) as they often experience hyperglycemia due to immunosuppressive drugs. Effective glucose management is crucial to prevent complications and maintain graft function.

Successful use of the sodium-glucose co-transporter-2 inhibitor dapagliflozin in patients with renal transplant and diabetes: a case series and literature review.Efficacy and Safety of Empagliflozin in Renal Transplant Recipients With Posttransplant Diabetes Mellitus.