2025 AMA Research Challenge – Member Premier Access

October 22, 2025

Virtual only, United States

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Background: Obesity is a major risk factor for HFpEF. While glucagon-like peptide 1 (GLP-1) receptor agonists have demonstrated benefit in obesity-related HFpEF, access remains limited. Phentermine/topiramate is a cost-effective alternative, producing up to 13% body weight loss, but concerns about cardiovascular safety have limited its use.

Methods: We retrospectively studied patients with obesity-related HFpEF treated with phentermine/topiramate. Outcomes included mean weight loss, proportion achieving >10% weight loss, changes in cardiometabolic parameters, and safety events. Data were collected at baseline, 6 ± 1 months, and 12 ± 1 months of treatment.

Results: Thirty-four patients (mean age 62.9 ± 12.4 years; 64.7% female; body mass index (BMI) 41.84 ± 7 kg/m²) were included. At 12 months, weight decreased by 11.04 ± 11.51 kg (11.1%), and BMI by 4.11 ± 4.21 kg/m²; 38% lost >10% of body weight. Mean heart rate increased by 3.3 ± 13.67 bpm; systolic blood pressure decreased by 6.6 ± 14.9 mmHg. Lipid profiles and glycemic parameters showed modest improvement or minimal change. No major adverse cardiac events occurred, and side effects were minor.

Conclusion: In patients with obesity-related HFpEF, phentermine/topiramate was associated with meaningful weight loss and no major adverse cardiovascular events. The small increase in heart rate appears clinically insignificant and is similar to that reported with GLP-1 agonists. Given its safety and affordability, phentermine/topiramate may be a viable first-line or adjunctive therapy in this population.

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2025 AMA Research Challenge – Member Premier Access

Tanya Ramadoss

22 October 2025

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