GLP-1 Receptor Agonists and Acute Diabetes Complications in Adults with Type 1 Diabetes: A Target Trial Emulation

Abstract Background To evaluate the association between Glucagon-like peptide-1 receptor agonists (GLP-1RA) use and the risk of acute diabetes complications among adults with type 1 diabetes (T1D) who were eligible for anti-obesity medication (AOM) treatment. Methods We employed a target trial emulation using EHR data from the OneFlorida+ network (2014–2024) to investigate the association between GLP-1RA initiation and acute diabetes complications among adults with T1D. Eligible participants were adults with a diagnosis of T1D and who met clinical criteria for AOM treatment. GLP-1RA initiators were 1:1 matched to non-initiators using time-conditional propensity scores. The primary outcome was the occurrence of diabetic ketoacidosis (DKA). Secondary outcomes included severe hypoglycemia, all-cause hospitalizations, and emergency department (ED) visits. Cox proportional hazards models were utilized to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). We applied a causal learning approach to explore heterogeneous treatment effects. Findings The matched cohort included 651 GLP-1RA users and 651 non-users. For GLP-1RA users and non-users, the incidence rates were 13.5 vs. 21.8 per 1,000 person-years for DKA. Compared to non-users, GLP-1RA use was not significantly associated with incidence of DKA (HR 0.62 [95%CI 0.33-1.17]) or severe hypoglycemia (HR 0.52 [95%CI 0.17-1.55]); notably, GLP-1RA use was significantly associated with fewer hospitalizations (HR 0.74 [95%CI 0.62-0.90]) and ED visits (HR 0.73 [95%CI 0.57-0.92]). Interpretation Among adults with T1D and obesity, GLP-1RA use was not associated with an increased risk of DKA or severe hypoglycemia but was linked to fewer ED visits and hospitalizations. Funding The study was supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK) R01DK133465.