What is the mechanism of action of this treatment?

SGLT2 inhibitors, such as empagliflozin, work by blocking the sodium-glucose co-transporter 2 in the kidneys, which increases urinary glucose excretion and lowers blood glucose levels. GLP-1 receptor agonists enhance insulin secretion, inhibit glucagon release, and slow gastric emptying, which helps control blood sugar levels and can aid in weight loss. Insulin therapy directly supplements or replaces the insulin that the body is unable to produce sufficiently, ensuring glucose is taken up by cells for energy. These mechanisms are crucial for Type 2 Diabetes patients as they address different aspects of glucose regulation, providing comprehensive management of blood sugar levels and reducing the risk of complications.

What side effects are associated with this type of intervention?

SGLT2 inhibitors, such as empagliflozin, are associated with side effects including an initial decrease in eGFR, urinary tract infections, and mycotic infections. There is also a noted risk of lower limb amputations, particularly with canagliflozin. GLP-1 receptor agonists, like liraglutide and semaglutide, commonly cause gastrointestinal issues such as nausea and vomiting. Insulin therapy can lead to hypoglycemia and weight gain. Each treatment has its own profile of benefits and risks, which should be considered in consultation with a healthcare provider.

What prior FDA approvals exist?

The FDA has approved several SGLT2 inhibitors for the treatment of Type 2 Diabetes, including empagliflozin, canagliflozin, and dapagliflozin. These medications work by inhibiting the sodium-glucose co-transporter 2 in the kidneys, which reduces glucose reabsorption and increases glucose excretion in the urine. Clinical trials, such as the EMPA-REG OUTCOME trial for empagliflozin, have demonstrated significant cardiovascular benefits and glycemic control in patients with Type 2 Diabetes. Canagliflozin was evaluated in the CANVAS Program, which highlighted both its efficacy and some safety concerns, such as an increased risk of amputations. Dapagliflozin has been studied in the DECLARE-TIMI 58 trial, showing cardiovascular benefits without an increased risk of amputations. These approvals and studies underscore the role of SGLT2 inhibitors in managing Type 2 Diabetes, particularly in patients with cardiovascular comorbidities.

What other types of research exist?

Promising alternatives to Empagliflozin for Type 2 Diabetes patients include GLP-1 receptor agonists such as Semaglutide and Liraglutide, which have shown significant efficacy in glycemic control and cardiovascular benefits. Additionally, other SGLT2 inhibitors like Dapagliflozin and Canagliflozin remain viable options. Emerging treatments like Tirzepatide, a dual GIP and GLP-1 receptor agonist, are also showing promise in recent studies.

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SGLT2 Inhibitor

Empagliflozin for Kidney Transplant Complications (CREST-KT Trial)

Phase 2

Recruiting

Led By Myles Wolf, MD

Research Sponsored by Duke University

Eligibility Criteria Checklist

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

Must have

Estimated glomerular filtration rate (eGFR) equal to or greater than 30ml/min/1.73m squared at screening

Standard immunosuppression, including calcineurin inhibitor, Mycophenolate Mofetil or Sodium and a glucocorticoid

Must not have

Any other solid organ transplant

Greater than 2 urinary tract infections (UTI) over the 12 months prior to enrollment

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline, 6 months, 9 months, 12 months and 18 months

Summary

This trial is testing a medication called empagliflozin, which helps lower blood sugar, in kidney transplant patients. The study includes patients with and without type 2 diabetes to see if the medication can improve their health. Empagliflozin works by helping the kidneys remove extra sugar from the blood through urine. This medication has been shown to significantly reduce blood glucose levels and is well tolerated in patients with type 2 diabetes.

Who is the study for?

This trial is for kidney transplant recipients, with or without type 2 diabetes, who are 12-60 months post-transplant. They must be on standard immunosuppression and have a stable kidney function (eGFR ≥30). Excluded are those with recent severe rejection episodes, pregnant/nursing women, uncircumcised men, active heavy anticoagulant users, Type I diabetics, multiple organ transplants or high hemoglobin A1c levels.

What is being tested?

The CREST-KT study tests the effects of Empagliflozin (a diabetes medication) in kidney transplant patients. It's a double-blind trial where participants are randomly assigned to receive either Empagliflozin or a placebo. The ratio of drug to placebo is 2:1 among both diabetic and non-diabetic groups.

What are the potential side effects?

Potential side effects of Empagliflozin include urinary tract infections due to increased sugar in urine which bacteria feed on; dehydration because it causes the body to expel more water; low blood pressure; and ketoacidosis – a serious condition related to insulin levels.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My kidney function, measured by eGFR, is at least 30ml/min/1.73m^2.

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I am on standard drugs to suppress my immune system.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had a solid organ transplant.

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I have had more than 2 UTIs in the last year.

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I am currently taking SGLT2 inhibitors.

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I am not on blood thinners except for low-dose aspirin.

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I have had a genital infection in the last year.

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I have Type 1 diabetes.

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I have had a severe rejection reaction or a high rejection score.

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I am an uncircumcised man.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline, 6 months, 9 months, 12 months and 18 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline, 6 months, 9 months, 12 months and 18 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline, 6 months, 9 months, 12 months and 18 months for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Change in blood insulin level

Change in cardiac structure

Change in fasting blood sugar

+4 more

Trial Design

2Treatment groups

Active Control

Group I: Arm I: With Type II DiabetesActive Control2 Interventions

Kidney Transplant recipient with Type II diabetes, randomized to either Empagliflozin or a placebo.

Group II: Arm 2: Without DiabetesActive Control2 Interventions

Kidney Transplant recipient without Type II diabetes, randomized to either Empagliflozin or a placebo

0 / 10Eligibility criteria met

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

SGLT2 inhibitors, such as empagliflozin, work by blocking the sodium-glucose co-transporter 2 in the kidneys, which increases urinary glucose excretion and lowers blood glucose levels. GLP-1 receptor agonists enhance insulin secretion, inhibit glucagon release, and slow gastric emptying, which helps control blood sugar levels and can aid in weight loss. Insulin therapy directly supplements or replaces the insulin that the body is unable to produce sufficiently, ensuring glucose is taken up by cells for energy. These mechanisms are crucial for Type 2 Diabetes patients as they address different aspects of glucose regulation, providing comprehensive management of blood sugar levels and reducing the risk of complications.

A patient-centered approach to managing patients with type 2 diabetes.