Addition of Phentermine‐Topiramate to a Digitally Enhanced Lifestyle Intervention: A Double‐Blind Randomized Clinical Trial

OBJECTIVE: This study compared the effects of phentermine-topiramate-ER (mid-dose 7.5/46 mg) versus placebo on weight loss and cardiovascular disease (CVD) risk outcomes when used as an adjunct to a digitally enhanced lifestyle intervention (DELI). METHODS: ) were enrolled in the DELI program, consisting of in-person and telehealth modalities, dietary and physical activity goals, and use of a smartphone application integrated with digital devices (Apple Watch and Bluetooth-enabled weight scale and blood pressure monitor). Participants were randomized 1:1 to receive either phentermine-topiramate-ER (n = 42) or placebo (n = 38) in addition to the DELI. RESULTS: At 3 months, the phentermine-topiramate group lost a mean of 10.82 kg versus 4.04 kg in the placebo group (mean difference -6.78 kg; p = 0.002). At 12 months, weight loss was 15.32 kg versus 5.85 kg, respectively (mean difference -9.48 kg; p < 0.001). Participants receiving phentermine-topiramate-ER experienced a 3.35% reduction in the estimated atherosclerotic CVD risk compared to baseline (p = 0.004). CONCLUSIONS: Phentermine-topiramate-ER, when combined with a DELI, produced significant and sustained weight loss and reduced CVD risk in adults with obesity. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04408586.