DC2421 - Subcutaneous weekly semaglutide as adjunct to automated insulin delivery: a double-blinded, randomized, cross-over trial

Blinded Abstract: Background
No randomized controlled trial has assessed the efficacy and safety of subcutaneous semaglutide in type 1 diabetes.

Methods
We performed a randomized, placebo-controlled, cross-over trial to assess the glycemic efficacy and safety of semaglutide as add-on therapy to automated insulin delivery therapy. In each intervention, participants were titrated up to 1 mg of semaglutide or placebo over 11 weeks, followed by use of an automated insulin delivery system for 4 weeks. The interventions were separated by 2 weeks wash-out period. The primary outcome was percentage of time spent in the target glucose range of 3.9 to 10 mmol/L during the last 4 weeks of each intervention. Key secondary outcomes were time spent in below 3.9 mmol/L, weight, insulin usage, and HbA1c.

Results
Twenty-four of 28 participants (BMI 32.2 (SD 5.1) kg/m2, HbA1c 7.4 (0.8) %) completed the trial and were included in the analysis. Compared to placebo, semaglutide increased time in target range by mean 4.8 (SD 7.6) percentage points (p = 0.006), without increasing time spent below 3.9 mmol/L (p = 0.19). This coincided with a placebo-adjusted reduction in daily insulin by 15.8 (17.0) units, equating to 22.3% (18.4), reduction in weight by 5.3 (2.9) kg, equating to 5.1% (3.0), and reduction in HbA1c by 0.4% (0.4; p < 0.001 for all comparisons). There were 2 episodes of euglycemic ketosis without acidosis requiring medical assistance during semaglutide use.

Conclusions
Semaglutide improves glycemic control with automated insulin delivery compared to placebo, along with reductions in weight and insulin usage.