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[Preprint]. 2026 Feb 20:2026.02.18.26346594. [Version 1] doi: 10.64898/2026.02.18.26346594

Secondary Prevention of Cardiovascular Events in Patients with Overweight/Obesity in Routine Clinical Practice

Wenxin Guo, Maidou Wang, Jiwon Shin, Fan Li, Emily C O’Brien, LáShauntá Glover, Kristina Bortfeld, Anqi Zhao, Ryan McDevitt, Cheryl Kalapura, Sarah Wu, Sahar Shibeika, Shannon Aymes, Michael Porter, Brian Mac Grory, Jay B Lusk
PMCID: PMC12934895  PMID: 41757166

ABSTRACT

Background and Aims

The glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide has demonstrated efficacy for the secondary prevention of cardiovascular disease among patients with overweight/obesity without diabetes mellitus. However, the comparative effectiveness of GLP-1 RA versus other antiobesity medications (e.g. phentermine-topiramate) not been evaluated.

Methods

This was a retrospective, observational, cohort study using target trial emulation methodology using the Truveta electronic health record database of more than 120 million patients. Adult patients with a body mass index (BMI) >=27 kg/m 2 , a history of cardiovascular disease (prior ischemic stroke, transient ischemic attack, or myocardial infarction, or known coronary artery disease, heart failure, or peripheral artery disease) without diabetes mellitus were included in the study. The primary endpoint was time to first major adverse cardiovascular or cerebrovascular event (MACCE, defined as stroke or myocardial infarction).

Results

In total, 35,240 were included in the bupropion-naltrexone versus GLP-1 RA comparison, and 27,051 were included in the phentermine-topiramate versus GLP-1 RA comparison. In the pre-weighting cohort, GLP-1 RA use was associated with decreased hazard of MACCE compared to bupropion-naltrexone (HR 0.50 [95% confidence interval (CI) 0.36-0.69]) and phentermine-topiramate (HR 0.43 [95% CI 0.30-0.60]). In the propensity score-overlap weighted cohort, GLP-1 RA prescription was not associated with a lower hazard of MACCE than bupropion-naltrexone (aHR 0.69 [95% CI 0.47-1.00]) but was associated with a lower hazard compared to phentermine-topiramate (aHR 0.61 [95% CI 0.41-0.91]; adjusted absolute rate difference 0.98 per 1000 person-years).

Conclusions

Prescription of a GLP-1 RA was associated with a lower risk of subsequent MACCE than phentermine-topiramate.

Full Text Availability

The license terms selected by the author(s) for this preprint version do not permit archiving in PMC. The full text is available from the preprint server.


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