Effectiveness and Safety of Semaglutide in Type 1 Diabetes: A Danish Nationwide Cohort Study (2018-2024).

Abstract

Semaglutide is not approved for glycemic management in type 1 diabetes (T1D) due to limited evidence and safety concerns. Nevertheless, its use is increasing. We investigated glycemic and safety outcomes of semaglutide in a nationwide cohort of individuals with T1D. Using Danish registries (2018-2024), we identified individuals with T1D initiating semaglutide and matched them 1:4 using exposure density matching to unexposed control persons with T1D following them for up to two years. Glycemic trajectories were modeled using a piecewise mixed model. Cause-specific Cox models were used to estimate hospitalization rates for hypoglycemia and diabetic ketoacidosis compared with matched controls. Aalen-Johansen estimator was used to estimate adherence while accounting for death as a competing risk. We identified 879 individuals with T1D initiating semaglutide (multiple daily injections (MDI): n = 622; insulin pump: n = 257). HbA1c decreased by 5.7 mmol/mol (0.52%) (95% CI: 5.0-6.3) during the first six months and remained stable thereafter in semaglutide users while remaining unchanged in the control group. Compared with matched controls semaglutide use was not associated with an increased rate of hospitalization for hypoglycemia (HR 0.64; 95%CI: 0.35; 1.19) or diabetic ketoacidosis (HR 0.73; 95%CI; 0.34; 1.57). The cumulative probability of adherence to semaglutide at one year was 50% (95% CI: 47-54). No difference in HbA1c reduction from 0 to 6 months was observed between MDI compared to insulin pump users (P = 0.42). The median semaglutide dose redeemed during follow-up was 1.0 mg. In this nationwide cohort of individuals with T1D, semaglutide use was associated with no increased rate of hospitalization for hypoglycemia and no increased diabetic ketoacidosis rate, and a clinically meaningful reduction of HbA1c. This study received no funding.