Anastasios Tentolouris, Charalampos Filippatos, Nikolaos-Iason Tepetes, M Gavriatopoulou, Evangelos Terpos, Alexandros Briasoulis, K S Stamatelopoulos, Theodosios Filippatos
AIMS: Evidence on cardiovascular/renal outcomes associated with GLP-1-based therapies in type 1 diabetes (T1D) is limited. We examined the effects of GLP-1-based therapy on major clinical outcomes and safety, including diabetic ketoacidosis (DKA) and hypoglycemia risk, in adults with T1D in a large real-world cohort. MATERIALS AND METHODS: This retrospective cohort study utilised the TriNetX global health research network. Adults with T1D were classified by exposure to GLP-1-based therapies. Propensity score matching (1:1) balanced baseline characteristics for age, sex, demographic characteristics, cardiometabolic risk factors, comorbidities, medication use, and laboratory parameters including lipid profile and glycemic control. Outcomes included all-cause mortality, myocardial infarction, cerebral infarction, heart failure (HF), adapted major adverse cardiovascular events (MACE-all CV clinical outcomes), chronic kidney disease (CKD), and all-cause hospitalisation, plus safety outcomes (hypoglycemia and DKA). Event accrual began 6 months after therapy initiation. RESULTS: After matching, 4088 individuals per group were included. GLP-1-based therapy was associated with lower risks of all-cause mortality (HR 0.67, 95% CI 0.46-0.98), HF (HR 0.38, 95% CI 0.21-0.67), adapted-MACE (HR 0.61, 95% CI 0.40-0.94) and all-cause hospitalisation (HR 0.70, 95% CI 0.51-0.96). No significant differences were observed for myocardial infarction, ischemic stroke, or CKD. DKA incidence was not increased, while hypoglycemia risk was lower with GLP-1 therapy (HR 0.72, 95% CI 0.55-0.95). Less than 10 (0.2%) events of pancreatitis were noted in both groups. CONCLUSIONS: In this propensity score-matched real-world cohort of adults with T1D, GLP-1-based therapy was associated with lower risks of all-cause mortality, HF, adapted-MACE, hospitalisation, and hypoglycemia without increased DKA risk. Randomised controlled trials are needed to confirm these findings.