Overview

The goal of this 24 week double-blinded, randomized, parallel controlled clinical trial is to learn how semaglutide affects body composition in adults with type 1 diabetes and overweight/obesity.

The main question to answer is:

What effect does Semaglutide have on body composition in adults with type 1 diabetes and overweight/obesity compared to a placebo?

Around 40 participants will:

• Be randomly assigned to receive semaglutide or a placebo.
• Self-administer the treatment drug once per week for 24 weeks.
• Complete a series of tests, measurements and questionnaires throughout the study duration.
• Attend a remote follow-up visit 4 weeks after the treatment is complete.

Eligibility

Inclusion Criteria:

• Age 18-65 years old
• Clinical diagnosis of T1D (type 1 diabetes) for ≥ 1 year, as per clinician judgement.
• BMI (Body mass index) ≥ 27 kg/m2
• Use of multi-daily injections or insulin pump therapy.
• Use of CGM (continuous glucose monitoring).
• Agreement to the use of a highly effective method of birth control in persons of child-bearing age (if sexually active) and active avoidance of pregnancy during the trial. Child-bearing potential refers to participants of the female sex post-menarche who have not reached menopause or have a disclosed medical condition causing sterility (e.g. hysterectomy). Post-menopausal state refers to the absence of menses for 12 months without any alternative cause.
• Diabetic retinopathy assessment performed within the last 2 years, as per participant history.

Exclusion Criteria:

• Pre-existing conditions limiting physical activity, specifically inability to walk for 6 minutes.
• Active proliferative diabetic retinopathy requiring surgery or laser/injectable therapy within the last 3 months.

\If a history of proliferative retinopathy is present within the last year, written permission from the eligible participant's ophthalmologist or optometrist is required\

• HbA1c (glycated hemoglobin) ≥ 10% within the last 3 months.
• Current use of non-insulin anti-hyperglycemic agents within the last month.
• Severe hypoglycemic episode within the last 3 months, defined as an event where glycemia was \< 4 mmol/L, resulting in seizure, loss of consciousness, or need for third-party assistance in treatment.
• Diabetic ketoacidosis (DKA) within the last 3 months (DKA refers to the need to present to medical attention and the requirement of intravenous insulin due to ketones)
• History of bariatric surgery
• Personal history of acute/chronic pancreatitis or gallstone disease without cholecystectomy.
• Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2.
• Severe impairment of renal function with eGFR \<30 mL/min/1.73 m2 (using CKD-EPI formula), measured within the last 12 months.
• Use of supraphysiological doses of glucocorticoids in the last 3 months, and/or expected use at some point in the next 6 months.
• Planned or ongoing pregnancy
• Breastfeeding individuals
• Prior hypersensitivity reaction to GLP1-RA (glucagon-like-peptide-1 receptor agonist)
• Clinically significant gastroparesis, defined as persistent symptoms despite pharmacotherapy such as domperidone.
• Any prior diagnostic history of eating disorder or suicidal attempts, or feelings of suicidal thoughts or behaviours in the last month\*\*
• Unstable angina, or myocardial infarction/ cardiovascular surgery / coronary stenting in the last month.
• Any serious medical or psychiatric illness likely to interfere with study participation as per the judgment of the investigator (e.g. cirrhosis, active cancer, decompensated schizophrenia).