GLP-1 Receptor Agonist Therapy and Cardiorenal Outcomes in Type 1 Diabetes

Key Takeaways

• GLP-1-based therapy was associated with lower risks of all-cause mortality, heart failure, adapted MACE, and all-cause hospitalization in matched adults with type 1 diabetes.
• No significant differences were observed for myocardial infarction, ischemic stroke, or chronic kidney disease.
• Hypoglycemia was lower, DKA was not increased, pancreatitis events were rare in both groups, and the authors said randomized trials are needed.

In adults with type 1 diabetes, GLP-1-based therapy was associated with a lower heart failure risk in a recent study, with an HR of 0.38. The matched cohort also showed lower all-cause mortality, adapted MACE, and all-cause hospitalization, with several cardiovascular and utilization outcomes moving in the same direction. No significant difference was observed for chronic kidney disease, and diabetic ketoacidosis incidence was not increased. These findings reflect an observational comparison among matched adults with type 1 diabetes rather than a causal estimate.

The investigators conducted a retrospective cohort study using the TriNetX global health research network and classified adults with type 1 diabetes by GLP-1-based therapy exposure. One-to-one propensity score matching balanced 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, adapted MACE, chronic kidney disease, all-cause hospitalization, hypoglycemia, and DKA. After matching, 4,088 individuals were included in each group, and event accrual began 6 months after therapy initiation.

Several outcomes moved in the same direction, with lower risks for death, heart failure, adapted MACE, and all-cause hospitalization. All-cause mortality was lower with GLP-1-based therapy, with an HR of 0.67 and a 95% CI of 0.46 to 0.98. Heart failure showed an HR of 0.38 with a 95% CI of 0.21 to 0.67. Adapted MACE was lower as well, with an HR of 0.61 and a 95% CI of 0.40 to 0.94. All-cause hospitalization showed an HR of 0.70 with a 95% CI of 0.51 to 0.96.

No significant differences were observed for myocardial infarction, ischemic stroke, or chronic kidney disease in the matched analysis. Hypoglycemia risk was lower with GLP-1-based therapy, with an HR of 0.72 and a 95% CI of 0.55 to 0.95. Diabetic ketoacidosis incidence was not increased, and fewer than 10 pancreatitis events, or 0.2%, were noted in both groups. The authors concluded that randomized controlled trials are needed to confirm these observed associations.