Patients with type 2 diabetes and cardiovascular disease who consistently took their once-weekly GLP-1 medications had roughly 30% lower risk of heart attacks, strokes, and other major cardiovascular events.
HR 0.696 for MACEPersistent use of once-weekly GLP-1 drugs was associated with approximately 30% lower risk of major adverse cardiovascular events compared to non-persistent use.
What the researchers found
Among 29,516 patients with type 2 diabetes and atherosclerotic cardiovascular disease who started once-weekly GLP-1 receptor agonists, those who remained persistent with therapy had significantly lower cardiovascular risks compared to non-persistent patients:
- 2-point MACE (major adverse cardiovascular events): HR 0.696 (95% CI: 0.626–0.774), representing a ~30% risk reduction
- Stroke: HR 0.668 (95% CI: 0.573–0.777), representing a ~33% risk reduction
- Myocardial infarction (heart attack): HR 0.710 (95% CI: 0.621–0.813), representing a ~29% risk reduction
All associations were statistically significant (p < 0.001). Persistent patients were followed for an average of 418 days, while non-persistent patients were followed for 741 days.
Why it matters
GLP-1 receptor agonists have been shown in clinical trials to reduce cardiovascular events, but real-world medication adherence is often poor. This study quantifies the cardiovascular cost of non-persistence: patients who stop or have gaps in their GLP-1 therapy miss out on approximately 30% of the cardiovascular protection these drugs can provide. This has implications for clinical counseling and insurance coverage policies.
How the study worked
This was a retrospective cohort study using the Optum Research Database (a large US claims database). Researchers identified patients who started once-weekly GLP-1 receptor agonists between January 2018 and November 2022. Patients were classified as persistent (no gap ≥60 days in medication supply after the first 3 months) or non-persistent. Time-varying Cox proportional hazards models with adjustment for confounders assessed the association between persistence and cardiovascular outcomes.
What this study cannot tell us
This is a retrospective observational study, so it cannot prove causation — patients who stay on medication may differ from those who stop in ways that independently affect cardiovascular risk (healthy adherer bias). The study used claims data, which may not capture all relevant clinical variables. Non-persistent patients had longer follow-up, which could introduce surveillance bias. Specific GLP-1 agents were not differentiated in the results.
How to read the evidence
This is a large retrospective cohort study using real-world claims data from nearly 30,000 patients. While the sample size is substantial and the statistical methods are appropriate, the observational design means confounding and healthy adherer bias cannot be fully excluded.
When this study was published
Published in 2025, this study uses data from 2018–2022 and reflects current real-world use patterns of once-weekly GLP-1 receptor agonists.
The bigger picture
As GLP-1 receptor agonists are increasingly recognized for cardiovascular protection beyond blood sugar control, understanding the real-world impact of treatment persistence becomes critical. This study adds to evidence that the cardiovascular benefits seen in clinical trials translate to real-world practice — but only for patients who stay on their medication. With GLP-1 drug shortages and high costs affecting access, these findings support efforts to maintain treatment continuity.
Questions still open
- What drives non-persistence with GLP-1 therapy — side effects, cost, supply issues, or other factors?
- Would similar cardiovascular benefits of persistence be seen with daily GLP-1 formulations or oral semaglutide?
- Could targeted interventions to improve GLP-1 adherence be cost-effective given the cardiovascular risk reduction observed?
Common questions
How much does stopping a GLP-1 drug increase heart risk?
What counts as 'non-persistent' with GLP-1 therapy?
Read the original research
Persistence with once-weekly glucagon-like peptide 1 receptor agonist therapy decreases the risk of major adverse cardiovascular events: A retrospective analysis of patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease.
Diabetes research and clinical practice, 223, 112162
Citation
Dunn, Tyler J; Zhu, Yong; Gronroos, Noelle N; Xie, Lin; Sargent, Andrew; Gamble, Cory; Billings, Liana K. (2025). Persistence with once-weekly glucagon-like peptide 1 receptor agonist therapy decreases the risk of major adverse cardiovascular events: A retrospective analysis of patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease.. Diabetes research and clinical practice, 223, 112162. https://doi.org/10.1016/j.diabres.2025.112162