Semaglutide in Type 1 Diabetes reduces HbA1c by **0.52%**; no increased DKA or hypoglycemia.

Managing Type 1 Diabetes (T1D) remains challenging, with many individuals struggling to achieve optimal glycemic control despite insulin therapy. While GLP-1 receptor agonists like semaglutide are highly effective in Type 2 Diabetes (T2D), their use in T1D is off-label due to limited evidence and concerns about increased risks of hypoglycemia or diabetic ketoacidosis (DKA). This study addresses the critical gap by providing real-world data on semaglutide's glycemic efficacy and safety profile as an adjunct to insulin in a large T1D cohort, informing clinical practice where off-label use is already occurring.

Researchers conducted a nationwide cohort study using Danish registries (2018-2024) to identify 879 individuals with Type 1 Diabetes who initiated semaglutide. These individuals were matched 1:4 using exposure density matching to unexposed control persons with T1D, with follow-up for up to two years. The cohort included patients on multiple daily insulin injections (MDI: n = 622) and insulin pumps (n = 257). Glycemic trajectories, specifically HbA1c, were modeled using a piecewise mixed model. Cause-specific Cox models were employed to estimate hospitalization rates for hypoglycemia and diabetic ketoacidosis compared with matched controls. Adherence was estimated using the Aalen-Johansen estimator, accounting for death as a competing risk.

In individuals with Type 1 Diabetes initiating semaglutide, HbA1c significantly decreased by 5.7 mmol/mol (0.52%) (95% CI: 5.0-6.3) during the first six months of treatment, remaining stable thereafter. In contrast, the HbA1c levels in the matched control group remained unchanged over the same period. Crucially, 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) when compared to matched controls. No significant difference in HbA1c reduction from 0 to 6 months was observed between MDI and insulin pump users (P = 0.42). The median semaglutide dose redeemed during follow-up was 1.0 mg. The cumulative probability of adherence to semaglutide at one year was 50% (95% CI: 47-54).