Patient-centred Intervention With Virtual Support for Obesity and Kidney Transplant Access

• Semaglutide (Drug), also known as Wegovy, Ozempic, Generic Semaglutide, Apo-Semaglutide, Semaglutide Injection: Maximum tolerated dose of semaglutide subcutaneously once weekly. Maximum dose of 2.0 mg.
• Virtual Weight Management Coaching (Behavioral), also known as Coaching, Weight Management: Virtual meeting with intervention coach once every 4 weeks for 6 months, where the coach will discuss the goals and progress with participant, nutritional advice, exercise advice, and motivational support.

Primary outcomes

• Change in Body Weight [Baseline to 26 weeks +/- 14 days]: Continuous measure of weight in kilograms assessed on calibrated clinic scales (dry weight for those receiving dialysis given fluid shifts)

Secondary outcomes

• Quality of Life - Kidney Disease Quality of Life 36-Item Short Form [Baseline to 26 weeks +/- 14 days]: Change in Kidney Disease Quality of Life (KDQOL-36) score across treatment arms. KDQOL-36 is scored on a 0-100 scale across five domains, with higher scores indicating better health-related quality of life.
• Health-Related Quality of Life - European Quality of Life 5 Dimensions, 5 Level (EQ-5D-5L) Questionnaire [Baseline to 26 weeks +/- 14 days]: Change in health-related quality of life measured using the European Quality of Life 5-Dimension, 5-Level questionnaire across treatment arms. A score of 11111 = no problems in any dimension (best), and a score of 55555 = extreme problems in all dimensions (worst).
• Change in Functional Status - Kidney Disease Quality of Life 36-Item Short form (KDQOL-36) [Baseline to 26 weeks +/- 14 days]: Change in functional status measured with KDQOL-36™ scores across treatment arms. KDQOL-36 is scored on a 0-100 scale across five domains, with higher scores indicating better health-related quality of life.
• Change in Functional Status - European Quality of Life five-dimensional, five-level generic measure (EQ-5D-5L) scores across treatment arms. [Baseline to 26 weeks +/- 14 days]: Measured via EQ-5D-5L (European Quality of Life five-dimensional, five-level generic measure) scores across treatment arms. A score of 11111 = no problems in any dimension (best), and a score of 55555 = extreme problems in all dimensions (worst).
• Weight Loss ≥5% [Baseline to 26 weeks +/- 14 days]: Percentage of participants achieving at least 5% reduction in body weight from baseline.
• Weight Loss ≥10% [Baseline to 26 weeks +/- 14 days]: Percentage of participant achieving at least 10% reduction in body weight from baseline.
• Weight Loss ≥15% [26 weeks +/- 14 days]: Percentage of participants achieving at least 15% reduction in body weight from baseline.
• Weight Loss ≥20% [Baseline to 26 weeks +/- 14 days]: Percentage of participants achieving at least 20% reduction in body weight from baseline.
• Body Mass Index (BMI) [Baseline to 26 weeks +/- 14 days]: Change in BMI across treatment arms. Measured in kg/m²
• Body Surface Area (BSA) [Baseline to 26 weeks +/- 14 days]: Change in BSA across treatment arms. Measured in m².
• Body Mass Index <35 kg/m² [Week 26 +/- 14 days]: Percentage of participants achieving a BMI below <35 kg/m², corresponding to the specified weight-based threshold for transplant listing.
• Dalhousie Clinical Frailty Scale Rating [Baseline to 26 weeks +/- 14 days]: Change in Dalhousie Clinical Frailty Scale rating across treatment arms. The scale ranges from 1 (very fit) to 9 (terminally ill).
• SARC-F Score [Baseline to 26 weeks +/- 14 days]: Change in sarcopenia measured by SARC-F score across treatment arms. This questionnaire is scored out of 10, with a score of 4 or higher indicating probable sarcopenia.
• FRAIL Scale [Baseline to 26 weeks +/- 14 days]: Change in frailty measured by the FRAIL Scale across treatment arms. The scale scores five components - fatigue, resistance, ambulation, illnesses, and loss of weight - on a 0-5 scale, with 0 indicating robust, 1-2 pre-frail, and 3 or more indicating frailty.
• Acute Kidney Injury (AKI) [Baseline to 26 weeks +/- 14 days]: Incidence of AKI. AKI defined by KDIGO as creatinine ≥ 1.5x baseline within 7 days in non-dialysis participants
• Hypoglycemia [Baseline to week 26 +/- 14 days]: Incidence of hypoglycemia (blood glucose <4 mmol/L or time below target using continuous glucose monitoring)
• Gastrointestinal Symptoms [Baseline to 26 weeks +/- 14 days]: Incidence of gastrointestinal symptoms, including nausea, vomiting, constipation
• Acute Biliary Disease [Baseline to 26 weeks +/- 14 days]: Incidence of acute biliary disease.
• Acute Pancreatitis [Baseline to 26 weeks +/- 14 days]: Incidence of acute pancreatitis.
• Diabetic Retinopathy Interventions [Baseline to 26 weeks +/- 14 days]: Incidence of interventions for diabetic retinopathy
• Injection-site reactions [Baseline to 26 weeks +/- 14 days]: Incidence of injection-site reactions in the intervention arm.
• Malignant Neoplasms [Baseline to 26 weeks +/- 14 days]: Incidence of malignant neoplasms.
• Coaching Visit Adherence [Baseline to 26 weeks +/- 14 days]: Percentage of participants completing ≥4 of 6 coaching visits.
• Semaglutide Discontinuation [Baseline to 26 weeks +/- 14 days]: Percentage of participants discontinuing semaglutide in the intervention arm.
• Achievement of semaglutide dose ≥1.0 mg/week [Week 26 +/- 14 days]: Percentage of participants in the intervention group achieving a semaglutide dose of ≥1.0 mg/week.
• Achievement of Semaglutide Dose ≥2.0 mg/week [26 weeks +/- 14 days]: Percentage of participants achieving a semaglutide dose of ≥2.0 mg/week
• Semaglutide Initiation in Usual Care [Baseline to 26 weeks +/- 14 days]: Percentage of usual care arm participants initiating semaglutide during the study period.
• Use of Semaglutide in Usual Care Participants [Baseline to 26 weeks +/- 14 days]: Percentage of participants using semaglutide in the usual care arm.
• Semaglutide Dose ≥1.0 mg/Week in Usual care Arm [26 weeks +/- 14 days]: Percentage of usual care participants achieving semaglutide dose ≥1.0 mg/week
• Semaglutide Dose ≥2.0 mg/Week in Usual Care Arm [26 Weeks +/- 14 days]: Percentage of usual care participants achieving semaglutide dose ≥2.0 mg/week
• Body Fat Percentage Measured with Smart Scale [Baseline to 26 weeks +/- 14 days]: Change in body fat percentage among the subsample of intervention participants using the study smart scale.
• Muscle Mass Measured with Smart Scale [Baseline to 26 weeks +/- 14 days]: Measured in kilograms. Change in muscle mass among the subsample of intervention participants using the study smart scale.
• Intervention Costs [Baseline to 26 weeks]: The total cost of the intervention incurred by participants during the 26-week follow-up period, in Canadian dollars (CAD)
• Out-of-pocket costs [Baseline to 26 weeks]: Total out-of-pocket costs incurred by participants during the 26-week study period-including costs directly related to the intervention. Measured in Canadian dollars (CAD)
• Lost Productivity Costs [Baseline to 26 weeks]: Costs associated with productivity losses during the 26-week follow-up period, including costs directly related to the participant's health care and intervention. Measured in Canadian dollars (CAD)
• Health care utilization costs [Baseline to 26 weeks]: Total costs associated with health care utilization during the study period, including physician visits, hospitalizations, emergency department visits, medications, allied health services. Measured in Canadian dollars (CAD) using provincial administrative health data.

Other outcomes

• Change in HbA1c [Baseline to 24 Months]: Change in glycated hemoglobin among participants with diabetes across treatment arms.
• Hospitalization for Hyperglycemia [Baseline to 24 Months]: Incidence of hospitalization for hyperglycemia in participants with diabetes across treatment arms
• Hospitalization for hypoglycemia [Baseline to 24 Months]: Incidence of hospitalization for hypoglycemia in participants with diabetes across treatment arms.
• Initiation of Dialysis [Baseline to 24 Months]: Percentage of non-dialysis participants initiating dialysis across treatment arms
• Cardiovascular Composite [Baseline to 24 Months]: Composite of hospitalization for acute myocardial infarction, stroke, amputation, or heart failure across treatment arms.
• Kidney Transplantation [Baseline to 24 months]: Percentage of participants receiving kidney transplantation across treatment arms.
• Healthcare utilization [24 months]: Health care utilization over 24 months including number of hospital admissions, emergency department, outpatient and primary care visits, specialist visits, rehabilitation, allied health care visits. Measured using provincial administrative health data.
• Health care costs [24 months]: Health care costs over 24 months, including total health care costs, hospitalization-related costs, emergency department costs, outpatient and physician costs, medication costs. Measured in Canadian dollars (CAD) using provincial administrative health data.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* 18 years or older
* BMI >35 kg/m2
* eGFR <15ml/min/1.73m2 at baseline OR 2-year KFRE2 of 10% or greater

Exclusion Criteria:

* Known contraindication to a GLP-1RA (pancreatitis, personal or family history of medullary thyroid cancer, hypersensitivity, pregnancy, breastfeeding)
* Type 1 diabetes

• Kristin Clemens, MD, Principal investigator, St. Joseph's Health Care London, Western University
• Louise Moist, MD, Principal investigator, London Health Sciences Centre