787-P: Reducing Cardiometabolic Risk with Semaglutide in Type 1 Diabetes (RESET1)—A Double-Blinded Randomized Placebo-Controlled Trial (Study Protocol)

Background: Therapies are needed to address excess cardiovascular risk in type 1 diabetes. Once-weekly semaglutide, a long-acting glucagon-like peptide-1 receptor agonist, has been shown to improve weight, glycemia and reduce cardiovascular events in type 2 diabetes and obesity. Semaglutide may offer cardiometabolic protective benefits in type 1 diabetes. The REducing cardiometabolic risk with SEmaglutide in Type 1 diabetes (RESET1) study is a double-blind randomized, placebo-controlled trial of semaglutide in T1D.

Methods: We will study 60 adults aged 25-70 years with type 1 diabetes (duration >2 years), body mass index ≥25 kg/m², HbA1c ≥ 7% and at least 1 cardiovascular risk factor (microalbuminuria, hypertension or anti-hypertensive treatment, hyperlipidemia or lipid-lowering therapy, current smoking). Subjects will be randomized to semaglutide, titrated to 1.0mg weekly or volume-matched placebo for 26 weeks (supplied by Novo Nordisk A/S). The primary endpoint is carotid femoral pulse wave velocity, a measure of arterial stiffness and surrogate measure of cardiovascular risk. We will measure change in insulin sensitivity determined by hyperinsulinemic-euglycemic clamp; and incretin and pancreatic hormone action measured during mixed meal tolerance test to explore predictors and mechanisms for metabolic improvements. The trial is registered (Australian New Zealand Clinical Trial Registry, ACTRN12623001277639) and will be conducted in Sydney, Australia.

Conclusion: The RESET1 study will establish the effect of semaglutide on cardiometabolic health in adults with type 1 diabetes.