Intervention: Semaglutide
Trial phase: Phase 3
ATC code: A10BJ06
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Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 7
Group description: This arm will receive semaglutide.

Semaglutide 2 mg/1.5 ml (1.34 mg/ml), prefilled pen-injector for subcutaneous injection solution: 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.
Eligibility criteria:
Inclusion Criteria:

- Age ≥ 18 years
- BMI 25-45 kg/m2
- T2DM
- 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).
- 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].
- Ability to provide informed consent before any trial-related activities

- 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)

- Active malignancy
- History of pancreatitis
- Active substance abuse
- Severe COPD
- Pulmonary fibrosis
- Symptomatic angina or recent myocardial infarction within 6 months
- Severe peripheral vascular disease
- Cirrhosis
- New York Health Association (NYHA) Class III-IV congestive heart failure
- Severe cognitive impairment
- Drug addiction
- History of non-adherence to therapy
- Active infection

- Expected life expectancy < 5 years

Additional exclusion criteria

- Type 1 diabetes mellitus
- History of diabetic ketoacidosis within the last 12 months
- Planning on undergoing bariatric surgery in next 9 months.
- Pregnant, breast-feeding, or planned pregnancy prior to the end of participation or not using adequate contraceptive measures
- Self-reported average consumption of > 21 alcoholic beverages per week or binge drinking
- Psychiatric hospitalization in past year
- Principal investigator discretion (i.e. concerns about safety, compliance)
- Known or suspected allergy to trial medication
- Previous participation (i.e. randomized) in this trial
- Use of GLP1-RA or pramlintide within 90 days prior to screening
- Use of metformin (contraindicated with eGFR < 30 ml/min/1.73m2)
- Use of DPP-4 inhibitors within 30 days prior to screening
- Personal or family history of medullary thyroid cancer, multiple endocrine neoplasia types 2A and 2B syndrome
- Last hemoglobin A1c ≥ 12% or A1c <6% (to avoid risk of hypoglycemia) prior to screening