effect of subcutaneous semaglutide on kidney transplant candidacy

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

Summary: 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.

Eligibility criteria:
inclusion criteria: 1. - age ≥ 18 years 2. - bmi 25-45 kg/m2 3. - t2dm 4. - advanced ckd\* (last egfr \ 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

Keywords: ckd obesity kidney transplant transplant wait list diabetic kidney disease glp-1 semaglutide