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A study published in Nature Medicine evaluated whether glucagon-like peptide-1 receptor agonists (GLP-1RAs) are associated with cardiovascular and kidney outcomes in people with type 1 diabetes, a population not included in several landmark trials of the drug class. Yunwen Xu and colleagues used national electronic health record data and target trial emulation, an observational method designed to approximate aspects of a randomized trial.
The analysis used the Optum Labs Data Warehouse and included 174,678 patients with type 1 diabetes who were followed from January 2013 through March 2024, contributing more than six million person-trials. After propensity score weighting to balance measured characteristics between groups, GLP-1RA initiation was associated with a lower five-year risk of major adverse cardiovascular events, at 4.3% versus 5.0%, with a hazard ratio of 0.85. It was also associated with a lower risk of end-stage kidney disease, at 1.6% versus 1.9%, with a hazard ratio of 0.81.
Secondary outcomes were generally consistent with the primary findings. GLP-1RA initiation was associated with lower risks of hospitalization for heart failure and major adverse liver events, as well as greater weight loss. In the safety analysis, GLP-1RA initiation was not associated with increased risks of hospitalization for diabetic ketoacidosis or severe hypoglycemia, two outcomes of concern in type 1 diabetes.
The findings may be relevant to coverage decisions because GLP-1RAs are widely used and reimbursed in type 2 diabetes and obesity but are not approved for cardiorenal protection in type 1 diabetes, where use remains off-label. The authors concluded that the results support further evaluation of GLP-1RAs in this population and noted that large randomized trials are needed to confirm clinical benefit and safety.
