While glucagon-like peptide-1 receptor agonists (GLP-1RAs) have established cardiorenal benefits in type 2 diabetes, long-term data for their use in patients with type 1 diabetes (T1D) have been scarce. A new large-scale study suggests that initiating GLP-1RA therapy is associated with a lower risk of major adverse cardiovascular and kidney outcomes in this population, without compromising safety.¹

Methodology

This study was a sequential target trial emulation using national electronic health record data from the Optum Labs Data Warehouse in the US. The analysis included 174,678 patients with T1D from January 2013 to March 2024. Researchers compared outcomes between patients initiating a GLP-1RA and those not initiating the therapy (non-initiators). After propensity score weighting to balance baseline characteristics, the median follow-up was 38 months.¹

The primary outcomes were a composite of major adverse cardiovascular events (MACEs; myocardial infarction, stroke, or all-cause mortality) and end-stage kidney disease (ESKD; dialysis or kidney transplantation). Secondary outcomes included hospitalisation for heart failure (HF) and major adverse liver events.¹

Results

GLP-1RA initiation was associated with a significantly lower risk of MACEs compared with non-initiation. The 5-year risk of MACEs was 4.3% in the GLP-1RA group versus 5.0% in the non-initiation group (risk difference: -0.7%; 95% CI: -1.2% to -0.2%; HR: 0.85; 95% CI: 0.77–0.95).¹

Similarly, the risk of ESKD was lower for GLP-1RA initiators, with a 5-year risk of 1.6% versus 1.9% for non-initiators (risk difference: -0.3%; 95% CI: -0.6% to 0%; HR: 0.81; 95% CI: 0.69–0.95).¹

Regarding secondary outcomes, GLP-1RA use was linked to a lower risk of hospitalisation for HF (HR: 0.82; 95% CI: 0.71–0.94) and major adverse liver events (HR: 0.72; 95% CI: 0.60–0.85).¹

Importantly, the study found no increased risk of hospitalisation for diabetic ketoacidosis (DKA) or severe hypoglycaemia with GLP-1RA initiation.¹

Interpretation

This large observational study provides real-world evidence on the long-term effects of GLP-1RAs in T1D, a population at high risk for cardiorenal complications.² The authors concluded, “These findings suggest that GLP-1RAs may be beneficial against major adverse cardiorenal events in patients with type 1 diabetes, without compromising safety.”¹ The benefits appeared consistent across different age groups and baseline HbA1c levels.

Next Steps

The study authors note that large-scale randomised controlled trials are warranted to confirm these findings in patients with T1D.¹

This study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.

Disclaimer

The information presented in this article is for educational purposes only. Any quotes included reflect the opinions of the individual quoted, and do not necessarily reflect the views of the publisher. The publisher does not guarantee the accuracy or completeness of the content and accepts no responsibility for any errors, or any consequences arising from its use.

References

1. Xu Y, Malek ND, Chang AR, et al. Glucagon-like peptide-1 receptor agonists for major cardiovascular and kidney outcomes in type 1 diabetes. Nat Med 2026. https://doi.org/10.1038/s41591-026-04274-0

2. Kristófi R, Bodegard J, Gudbjörnsdottir S, et al. Cardiovascular and renal disease burden in type 1 compared with type 2 diabetes: a two-country nationwide observational study. Diabetes Care 2021;44:1211–18. https://doi.org/10.2337/dc20-2839