Background: Once-weekly semaglutide is approved for the management of type 2 diabetes and obesity. The efficacy and safety of semaglutide in adults with type 1 diabetes are not established.
Methods: In this 26-week, double-blind trial, we randomly assigned 72 adults with type 1 diabetes using an automated insulin delivery (AID) system and with a body mass index of 30 or higher in a 1:1 ratio to receive once-weekly semaglutide up to 1 mg or placebo. The primary composite end point consisted of achieving all of the following elements: continuous glucose monitoring (CGM)-based time between 70 and 180 mg/dl of greater than 70% and time below 70 mg/dl of less than 4%; and weight reduction of at least 5%.
Results: A significantly greater percentage of patients in the semaglutide group than in the placebo group achieved the primary composite outcome (36% vs. 0%; between-group difference, 36 percentage points; 95% confidence interval [CI], 20.6 to 52.2; P<0.001). The difference in the least-squares mean change from baseline to week 26 for the semaglutide versus placebo group for glycated hemoglobin was -0.3 percentage points (95% CI, -0.6 to -0.05), for percentage of time with CGM glucose levels between 70 and 180 mg/dl it was 8.8 percentage points (95% CI, 3.9 to 13.7), and for body weight it was -8.8 kg (95% CI, -10.6 to -7.0). There were two severe hypoglycemia events in each group, and no diabetic ketoacidosis was reported.
Conclusions: In adults with type 1 diabetes and obesity, semaglutide treatment, compared with AID use alone, significantly improved achievement of a composite of time in range of greater than 70%, with time below range of less than 4%, and a 5% body weight reduction. (Funded by Breakthrough T1D [Type 1 Diabetes]; ADJUST-T1D trial ; Clinicaltrials.gov number, NCT05537233).