Effect of Subcutaneous Semaglutide on Kidney Transplant Candidacy

Phase 3TerminatedNCT04741074

Geisinger Clinic15 enrolled

Overview

This randomized study evaluates the effect of subcutaneous semaglutide /in combination with lifestyle counseling in patients with type 2 diabetes mellitus (T2DM), overweight/obesity, and stage 4-5 chronic kidney disease (CKD) or dialysis-dependent end-stage kidney disease (ESKD) on patients' eligibility for kidney transplantation at the end of 9 months.

Transplant policies regarding listing consider uncontrolled diabetes and severe obesity to be contraindications though there is great variability for exact BMI (35-45 kg/m2) and A1c (9-10%) thresholds for listing by center. Glucagon-lowering peptide-1 receptor agonists (GLP-1 RAs) offer great promise in this population as they have been shown to reduce weight, central adiposity, A1c, and risk of cardiovascular outcomes with similar effects in patients with and without CKD. In this double-blind, placebo-controlled randomized controlled trial, the investigators will evaluate the effect of subcutaneous semaglutide 1.34 mg/ml (up to 1.0 mg per week) in combination with lifestyle counseling in patients with T2DM, overweight/obesity, and stage 4-5 CKD or dialysis-dependent ESKD on patients' eligibility for kidney transplantation in terms of diabetes control (A1c \<9%) and obesity (BMI \<35 kg/m2 or 35-40 kg/m2 with waist circumference \<120 cm) at the end of 9 months.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

CKD Diabetic Kidney Disease Type 2 Diabetes Mellitus in Obese Obesity Severe Obesity

Interventions

Semaglutide 2 mg/1.5 ml (1.34 mg/ml), prefilled pen-injector for subcutaneous injection solutionDRUG

Dose will be started at 0.25 mg per week. Dose escalation will occur every 4 weeks to mitigate risk of gastrointestinal side effects to a maximum dose of 1.0 mg per week.

Placebo 1.5 ml, prefilled pen-injector for subcutaneous injection solutionDRUG

Matched placebo solution for injection will be provided by Novo Nordisk in a 1.5 ml pre-filled pen-injector for subcutaneous injection with the same instructions on dose escalation.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. \- Age ≥ 18 years 2. \- BMI 25-45 kg/m2 3. \- T2DM 4. \- Advanced CKD\* (last eGFR \<30 ml/min/1.73m2 in EHR or ESKD on dialysis prior to screening) or stage G3B/A2-3 CKD (eGFR 30 to \<45 ml/min/1.73m2 with albumin/creatinine ratio \>30 mg/g). 5. \- Fulfill kidney transplant listing criteria except for one or more of the following reasons (1: uncontrolled diabetes \[A1c ≥9%); 2: severe obesity (BMI ≥ 40 kg/m2 or BMI 35-40 kg/m2 with waist circumference \>120 cm). See exclusion criteria for general contraindications used for transplant listing used by majority of U.S. transplant centers\]. 6. \- Ability to provide informed consent before any trial-related activities 7. \- Access to a telephone * The cause of the CKD does not need to be due specifically to diabetes Exclusion Criteria (General contraindications used for transplant listing used by majority of U.S. transplant centers) 1. \- Active malignancy 2. \- History of pancreatitis 3. \- Active substance abuse 4. \- Severe COPD 5. \- Pulmonary fibrosis 6. \- Symptomatic angina or recent myocardial infarction within 6 months 7. \- Severe peripheral vascular disease 8. \- Cirrhosis 9. \- New York Health Association (NYHA) Class III-IV congestive heart failure 10. \- Severe cognitive impairment 11. \- Drug addiction 12. \- History of non-adherence to therapy 13. \- Active infection 14. \- Expected life expectancy \< 5 years Additional exclusion criteria 15. \- Type 1 diabetes mellitus 16. \- History of diabetic ketoacidosis within the last 12 months 17. \- Planning on undergoing bariatric surgery in next 9 months. 18. \- Pregnant, breast-feeding, or planned pregnancy prior to the end of participation or not using adequate contraceptive measures 19. \- Self-reported average consumption of \> 21 alcoholic beverages per week or binge drinking 20. \- Psychiatric hospitalization in past year 21. \- Principal investigator discretion (i.e. concerns about safety, compliance) 22. \- Known or suspected allergy to trial medication 23. \- Previous participation (i.e. randomized) in this trial 24. \- Use of GLP1-RA or pramlintide within 90 days prior to screening 25. \- Use of metformin (contraindicated with eGFR \< 30 ml/min/1.73m2) 26. \- Use of DPP-4 inhibitors within 30 days prior to screening 27. \- Personal or family history of medullary thyroid cancer, multiple endocrine neoplasia types 2A and 2B syndrome 28. \- Last hemoglobin A1c ≥ 12% or A1c \<6% (to avoid risk of hypoglycemia) prior to screening

Locations (2)

Geisinger Medical Center

Danville, Pennsylvania, United States

Geisinger Wyoming Valley

Wilkes-Barre, Pennsylvania, United States

Outcomes

Primary Outcomes

Kidney Transplant Eligibility

Proportion either listed for kidney transplant at 9 months or meeting the following kidney transplant candidacy criteria for A1c (\<9%) and obesity (BMI \<35 kg/m2 or BMI 35-40 kg/m2 with waist circumference \<120 cm)

Time frame: Ascertained at the end of 9 months

Secondary Outcomes

Change in Hemoglobin A1c (HgbA1c)

HgbA1c will be collected using routine procedures and measured on the same day at the central Geisinger laboratory by Turbidimetric inhibition immunoassay.