GLP-1 receptor agonists were associated with 39% lower risk of cardiovascular events compared to phentermine-topiramate in non-diabetic patients with obesity and existing cardiovascular disease.
39% CV risk reductionGLP-1 drugs significantly outperformed phentermine-topiramate for preventing heart attacks and strokes in obese non-diabetic CVD patients
What the researchers found
GLP-1 RA vs phentermine-topiramate: aHR 0.61 (95% CI 0.41-0.91) for MACCE. GLP-1 RA vs bupropion-naltrexone: aHR 0.69 (95% CI 0.47-1.00, borderline). 35,240 and 27,051 patients in comparisons.
Why it matters
Multiple weight loss drugs are available, but only GLP-1 drugs have shown cardiovascular event reduction. This head-to-head comparison quantifies the advantage.
How the study worked
Retrospective target trial emulation using Truveta EHR database (120M+ patients), propensity score-overlap weighting, comparing GLP-1 RA to bupropion-naltrexone and phentermine-topiramate in non-diabetic adults with BMI ≥27 and CVD history.
What this study cannot tell us
Observational despite target trial emulation. Cannot completely eliminate confounding. Short-term follow-up for some outcomes. Non-diabetic population only.
How to read the evidence
Large observational study with target trial emulation methodology — the highest quality achievable without an RCT. Consistent with SELECT trial findings.
When this study was published
Published in 2025 using Truveta database.
The bigger picture
This provides the evidence needed for formulary decisions: GLP-1 drugs should be preferred for cardiovascular secondary prevention over other weight loss medications.
Questions still open
- Should GLP-1 drugs be mandatory first-line for all obese CVD patients?
- Does the CV benefit extend to patients without prior CVD?
- Would head-to-head RCTs confirm these findings?
Common questions
Which weight loss drug is best for heart protection?
Do other weight loss drugs protect the heart?
Read the original research
Secondary Prevention of Cardiovascular Events in Patients with Overweight/Obesity in Routine Clinical Practice.
medRxiv : the preprint server for health sciences
Citation
Guo, Wenxin; Wang, Maidou; Shin, Jiwon; Li, Fan; O'Brien, Emily C; Glover, LáShauntá; Bortfeld, Kristina; Zhao, Anqi; McDevitt, Ryan; Kalapura, Cheryl; Wu, Sarah; Shibeika, Sahar; Aymes, Shannon; Porter, Michael; Grory, Brian Mac; Lusk, Jay B. (2026). Secondary Prevention of Cardiovascular Events in Patients with Overweight/Obesity in Routine Clinical Practice.. medRxiv : the preprint server for health sciences. https://doi.org/10.64898/2026.02.18.26346594