Effects of phentermine / topiramate extended-release, phentermine, and placebo on ambulatory blood pressure monitoring in adults with overweight or obesity: A randomized, multicenter, double-blind study.

Background: A fixed-dose combination of phentermine and extended-release topiramate (PHEN/TPM - approved for weight management) has demonstrated in-clinic reduction of blood pressure (BP). Ambulatory BP monitoring (ABPM) may be a better predictor of cardiovascular disease risk than in-clinic BP.
Methods: This randomized, multicenter, double-blind study enrolled 565 adults with overweight/obesity. Inclusion criteria included participants willing to wear ABPM device for 24 h. Exclusion criteria included screening blood pressure >140/90 mmHg and antihypertensive medications not stable for 3 months prior to randomization. Participants received placebo (n = 184), phentermine 30 mg; (n = 191), or PHEN 15 mg/TPM 92 mg; (n = 190). 24-hour ABPM was performed at baseline and at week 8. The primary endpoint was mean 24-h systolic BP (SBP) as measured by ABPM, in the per protocol population.
Results: Participants were mostly female (73.5 ​%) and White (81.6 ​%), with a mean age of 53.4 years; 32.4 ​% had no hypertension diagnosis or treatment, 62.5 ​% had hypertension using 0 to 2 antihypertensive medications, and 5.1 ​% had hypertension using ≥ 3 antihypertensive medications. Baseline mean SBP/diastolic BP (DBP) was 123.9/77.6 ​mmHg. At week 8, mean SBP change was -0.1 ​mmHg (placebo), +1.4 ​mmHg (phentermine 30 ​mg), and -3.3 ​mmHg (PHEN/TPM). Between-group difference for PHEN/TPM versus placebo was -3.2 ​mmHg (95 ​% CI: -5.48, -0.93 ​mmHg; p ​= ​0.0059). The between-group difference for PHEN/TPM versus phentermine 30 ​mg was -4.7 ​mmHg (95 ​% CI: -6.96, -2.45 ​mmHg; p ​< ​0.0001). Common (>2 ​% in any treatment group) adverse events (i.e., dry mouth, constipation, nausea, dizziness, paresthesia, dysgeusia, headache, COVID-19, urinary tract infection, insomnia, and anxiety) were mostly mild or moderate.
Conclusions: In this randomized, multicenter, double-blind ABPM study, PHEN/ TPM reduced SBP compared to either placebo or phentermine 30 mg (Funding: Vivus LLC; ClinicalTrials.gov: NCT05215418).
Competing Interests: HEB's research site institution has received research grants from 89Bio, Alon Medtech/Epitomee, Altimmune, Amgen, Boehringer Ingelheim, Eli Lilly, Kallyope, Novartis, NovoNordisk, Pfizer, Shionogi, Viking, and Vivus. HEB has served as a consultant/advisor for 89Bio, Altimmune, Amgen, Boehringer Ingelheim, and Lilly. DSH served as a site principal investigator for this study, which was conducted through a contract with his institution. DSH did not receive any funds directly from the sponsor. LTN is a full-time employee of VIVUS LLC, which markets the PHEN/TPM product evaluated in this study. At the time of this study her work on this study was done as part of her employment. CAP is a full-time employee of VIVUS LLC, which markets the PHEN/TPM product evaluated in this study. At the time of this study, his work on this study was done as part of his employment. STV is a full-time employee of VIVUS LLC, which markets the PHEN/TPM product evaluated in this study. At the time of this study, his work on this study was done as part of his employment and role as an officer in the company.
(© 2024 The Authors.)