The study aims to determine the short-term efficacy, mechanisms and safety of 24 weeks of placebo and semaglutide therapy in 74 KTR at risk of post-transplant diabetes mellitus (PTDM).

A kidney transplant is the best treatment for people living with kidney failure as it allows people to live longer with a better quality of life. However, one in four kidney transplant recipients will develop diabetes after transplant. This is largely due to the medications that must be used to prevent rejection of the transplant. Kidney transplant recipients who get diabetes after transplant are up to three times more likely to have heart disease and die prematurely. To date, there are no treatments to prevent the development of diabetes after kidney transplant. Semaglutide is a drug that is commonly used to treat diabetes and obesity. The investigators believe that semaglutide is a safe and effective drug which can prevent the development of diabetes in kidney transplant recipients. Therefore, the investigators are conducting a study where kidney transplant recipients who are at increased risk of developing diabetes after transplant are randomly assigned to receive either semaglutide or placebo for 24 weeks after their transplant. The study will determine whether semaglutide is effective in decreasing blood sugar levels and the rate of diabetes. The investigators will also study other important markers of health including body weight and cholesterol levels as well as liver, kidney and heart function. Diabetes after transplant is a common problem, and preventing it is extremely important to allowing kidney transplant recipients to live longer and better lives. The results of this study will allow the investigators to determine if semaglutide is a safe and effective option for the prevention of diabetes in kidney transplant recipients.

Inclusion Criteria:

1. Signed and dated written informed consent.

2. Adult (≥18 years) recipients of a living or deceased donor kidney transplant

3. Between 4- and 12-weeks post kidney transplant

4. Stable kidney function defined as an eGFR > 30 ml/min/1.73m2 (CKD-EPI)

5. At risk for PTDM at the time of transplant based on the following criteria:

   1. BMI ≥ 25 kg/m2, or
   2. Fasting plasma glucose 6.1-6.9 mmol/L (impaired fasting glucose), or
   3. 2hr OGTT plasma glucose 7.8-11.0 (impaired glucose tolerance), or
   4. HbA1C 5.5-6.4% (at risk for DM or prediabetes).

Exclusion Criteria:

1. Established diagnosis of type 1 or type 2 DM as per Diabetes Canada (including the need for glucose-lowering therapy for hyperglycemia at the time of screening)
2. Kidney-Pancreas transplant recipient
3. Acute coronary syndrome, transient ischemic attack or stroke within 30 days prior to screening
4. History of pancreatitis
5. Personal or family history of medullary thyroid cancer or MEN2B
6. Women who are pregnant, nursing or plan on becoming pregnant whilst in the trial
7. Use of GLP1RA in the 30 days prior to screening
8. Contraindication to MRI (applicable only to those undergoing the optional MRI assessments)
9. With known or suspected hypersensitivity to semaglutide or related products
10. Patient not able to understand and comply with study requirements, based on Investigator's judgment.
11. Any other clinical condition that, based on Investigator's judgement, would jeopardize patient safety during trial participation or would affect the study outcom
12. History of glucose-galactose malabsorption syndrome