Subcutaneous weekly semaglutide with automated insulin delivery in type 1 diabetes: a double-blind, randomized, crossover trial

Efforts to improve glycemic control in type 1 diabetes are ongoing. We performed a randomized, double-blind, crossover trial to assess semaglutide as adjunct to automated insulin delivery therapy in adults with type 1 diabetes. At each intervention, participants were titrated up to 1 mg or the maximum tolerated dose of semaglutide or placebo over 11 weeks, followed by the use of an automated insulin delivery system for 4 weeks. The primary outcome was the percentage of time spent in the target glucose range of 3.9–10.0 mmol l−1 during the last 4 weeks of each intervention. Twenty-eight participants were randomized and 24 completed the trial. The primary endpoint was met. Compared to placebo, semaglutide increased time in the target range by a mean 4.8 (s.d. = 7.6) percentage points (P = 0.006), without increasing the time spent below 3.9 mmol l−1 (P = 0.19) or below 3.0 mmol l−1 (P = 0.65). While no diabetic ketoacidosis or severe hypoglycemia occurred during any of the interventions, there were two episodes of recurrent euglycemic ketosis without acidosis during semaglutide use. We conclude that semaglutide improves glycemic control with automated insulin delivery compared to placebo. ClinicalTrials.gov registration: NCT05205928 In a crossover trial evaluating semaglutide versus placebo as an add-on to automated insulin delivery therapy in adults with type 1 diabetes, the use of semaglutide was associated with an increased percentage of time spent within the target glucose range, along with reduced insulin requirements.