Glucagon-like-peptide-1 Receptor Agonists in Patients Receiving Maintenance Dialysis

This study aims to determine if GLP1RA is safe and tolerable in maintenance dialysis population, adherence, and feasibility of a larger definitive cardiovascular outcome trial in this population. Participants will be randomized 1:1 to either weekly subcutaneous semaglutide versus usual care and followed for 26 weeks.

In this randomized pilot study, Individuals randomized to the active intervention arm will take semaglutide once weekly. Semaglutide (injectable, 1.34 mg/mL) is delivered subcutaneously via a multiple-use pen-injector that can be used to dial in all required doses on the same pen-injector. The clinical pen has a drum scale of 1-80 in increments of 1. Participants will be trained/re-trained on injector use at 0, 4, 8, and 12 weeks. For participants receiving in-centre hemodialysis, the intervention may be administered during the dialysis session by nursing personnel. Semaglutide will be titrated using an algorithm used in previous trials with a starting dose of 0.25 mg/week, with an increase to 0.5 mg/week after 4 weeks, and to the maximum dose of 1.0 mg/week after 8 weeks as tolerated. If a participant experiences an adverse effect, efforts will be made to maintain the current dosage, with dose reductions or treatment pauses permitted at the discretion of the site investigator. Patient receiving concomitant insulin therapy will have therapy adjusted as per a pre-specified algorithm. Participants allocated to the usual care arm will receive usual care. Primary outcomes: 1. Feasibility of study recruitment: ≥ 40% of fully eligible patients consent to participate in the trial. 2. Adherence to intervention: ≥ 70% of enrolled patients are adherent to the study intervention over the 26-week follow-up period. 3. Ability to follow: ≥ 90% of participants will be successfully followed to week Secondary outcomes: * Proportion Discontinuing Intervention * Safety Events * Major Adverse Cardiovascular Outcomes (Cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or a peripheral arterial event) * Body Weight/BMI * Systolic/diastolic blood pressure * Insulin dosage, glycemic control (HbA1c and random glucose) * Lipid profile * Hemoglobin, Calcium, Phosphate, PTH * EQ-5D-5L for baseline-adjusted changes in quality of life and symptom burden