GLP-1 drugs and type 1 diabetes: what a 174,000-patient study found

Major GLP-1 cardiovascular outcome trials — LEADER (liraglutide), SUSTAIN-6 (semaglutide), REWIND (dulaglutide), SURPASS-CVOT (tirzepatide) — enrolled patients with type 2 diabetes and established or high cardiovascular risk. Type 1 diabetes was typically an exclusion criterion.

This is partly regulatory, partly practical (T1D is less common), and partly biological (the role of GLP-1 in T1D is less well-characterized). The result has been real clinical uncertainty about what GLP-1s do or don't do for T1D patients at cardiorenal risk.

If you need background on the drug classes referenced here, see our explainers on semaglutide and tirzepatide.

The study (PMID 41857198, doi:10.1038/s41591-026-04274-0) used national electronic health record data from 174,678 patients with type 1 diabetes across 60+ US health systems, from January 2013 to March 2024.

Researchers used a method called sequential target trial emulation — a rigorous approach designed to approximate the structure of a randomized trial using real-world data. After propensity score weighting to balance differences between the groups, they compared cardiovascular and kidney outcomes.

The study was led by Dr. Jung-Im Shin at the Johns Hopkins Bloomberg School of Public Health, with NIH/NIDDK funding. The authors declared no competing interests.

Major adverse cardiovascular events (MACE):

• 5-year risk in GLP-1 initiators: 4.3%
• 5-year risk in non-initiators: 5.0%
• Hazard ratio: 0.85 (95% CI 0.77–0.95)
• Risk difference: −0.7% (95% CI −1.2% to −0.2%)

End-stage kidney disease:

• 5-year risk in GLP-1 initiators: 1.6%
• 5-year risk in non-initiators: 1.9%
• Hazard ratio: 0.81 (95% CI 0.69–0.95)
• Risk difference: −0.3% (95% CI −0.6% to 0%)

Safety outcomes:

• No increased risk of hospitalization for DKA (HR numerically lower)
• No increased risk of hospitalization for severe hypoglycemia (HR numerically lower)
• Note: only hospitalized cases were captured — outpatient DKA or hypoglycemia events are not reflected in these estimates

The study also found lower rates of hospitalization for heart failure and major adverse liver events in the GLP-1 group, reported as secondary outcomes.

Two safety concerns arise specifically with GLP-1 use in type 1 diabetes:

Diabetic ketoacidosis (DKA): GLP-1s reduce appetite and can lead to lower carbohydrate intake. In T1D patients on insulin, this can theoretically contribute to DKA if insulin doses aren't adjusted. This concern has been debated in clinical literature.

Severe hypoglycemia: GLP-1s can increase hypoglycemia risk when used with insulin.

This study found no increased risk of hospitalized events for either. That's reassuring, but comes with an important caveat: the study only captured events severe enough to require hospitalization. Mild-to-moderate DKA and outpatient hypoglycemia would not appear in these results.

Sequential target trial emulation is rigorous — but it remains observational. Specific limitations:

• T1D can be misclassified in electronic health records
• GLP-1 use in T1D is off-label, meaning patients who received it may have had characteristics that differ from those who didn't (residual confounding)
• The study cannot establish causation — only association
• The research covers 2013–2024; the GLP-1 drugs and doses available changed significantly over that period

These limitations don't invalidate the findings — but they mean this evidence sits below the level of a randomized controlled trial. It is hypothesis-generating: strong enough to inform clinical conversations, not strong enough to drive guidelines on its own.

• Whether these findings would replicate in a randomized trial
• Whether GLP-1s should be part of standard T1D care — no major guidelines currently recommend this
• The optimal GLP-1 agent, dose, and patient selection criteria in T1D
• Long-term effects beyond the study period

• Given my specific cardiorenal risk profile, does this study change how you think about GLP-1s in my care?
• What would you monitor if I were to try an off-label GLP-1?
• Would any insulin dose adjustment be needed?
• Is there a clinical trial I could enroll in to access GLP-1 therapy in T1D with proper study-level monitoring?

This study provides the strongest observational evidence to date that GLP-1 receptor agonists may offer cardiorenal benefit to people with type 1 diabetes — and does not support the concern that they increase the risk of hospitalized DKA or severe hypoglycemia.

That is a meaningful contribution to a genuinely evidence-thin area. But GLP-1s are not approved for T1D, this is not RCT evidence, and whether GLP-1 therapy makes sense for any individual T1D patient is a conversation with their endocrinologist.

Bring this paper to your next appointment. Ask about it directly. That's the right use of this evidence.

Medical disclaimer: This content is for educational purposes only and is not medical advice. Always consult a licensed healthcare professional before starting, stopping, or changing any treatment.

Sources

• Shin JI et al. GLP-1 receptor agonists for major cardiovascular and kidney outcomes in type 1 diabetes. Nature Medicine, March 2026. PMID 41857198. doi:10.1038/s41591-026-04274-0. nature.com
• PubMed abstract (verified). pubmed.ncbi.nlm.nih.gov
• JHU Bloomberg School of Public Health press release. publichealth.jhu.edu