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

Nov 26, 2025medRxiv : the preprint server for health sciences

GLP-1 Receptor Drugs and Short-Term Diabetes Problems in Adults with Type 1 Diabetes

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Abstract

In a matched cohort of 651 adults with type 1 diabetes using GLP-1 receptor agonists, the incidence rate of diabetic ketoacidosis was 13.5 per 1,000 person-years compared to 21.8 for non-users.

GLP-1 receptor agonist use was not significantly associated with the incidence of diabetic ketoacidosis (HR 0.62 [95% CI 0.33-1.17]).
There was also no significant association between GLP-1 receptor agonist use and severe hypoglycemia (HR 0.52 [95% CI 0.17-1.55]).
GLP-1 receptor agonist users experienced fewer hospitalizations compared to non-users (HR 0.74 [95% CI 0.62-0.90]).
Emergency department visits were also reduced among GLP-1 receptor agonist users (HR 0.73 [95% CI 0.57-0.92]).

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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

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

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