Effect of Subcutaneous Semaglutide on Kidney Transplant Candidacy
Condition: CKD; Diabetic Kidney Disease; Type 2 Diabetes Mellitus in Obese; Obesity; Severe Obesity
MeSH terms: Kidney Diseases; Diabetic Nephropathies; Obesity; Diabetes Mellitus, Type 2; Obesity, Morbid
Intervention: Semaglutide 2 mg/1.5 ml (1.34 mg/ml), prefilled pen-injector for subcutaneous injection solution; Placebo 1.5 ml, prefilled pen-injector for subcutaneous injection solution
Intervention description: 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.; 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.
Intervention MeSH terms: Pharmaceutical Solutions
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: This is a placebo-controlled double-blind clinical trial. Study investigators and participants will be blinded to treatment allocation.
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ckd; obesity; kidney transplant; transplant wait list; diabetic kidney disease; glp-1; semaglutide

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.
    

Eligibility criteria:

        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