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

Abstract

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.

Fig. 1. Participant recruitment and retention.

CONSORT flow chart describing participant recruitment and retention. SC, subcutaneously.

Extended Data Fig. 1. Participants' insulin and carbohydrate changes over time.

Weekly changes in a) total daily insulin requirements (upper plot) and b) daily carbohydrate intake (lower plot) over the 11-week titration period on participants’ own pump therapy (n = 24). Square dots depict mean values, with bars depicting standard error.

Extended Data Fig. 2. Scatterplot correlations.

Depicted correlations via scatterplot with trendline as per Pearson correlation (n = 24), with two-sided analyses used as default. Dots are individual data points. a) Placebo-adjusted weight change with placebo-adjusted change in time-in-range (3.9–10.0 mmol/L). b) Placebo-adjusted weight change with placebo-adjusted HbA1c change. c) Baseline BMI with placebo-adjusted weight change.