The Long-Term Effectiveness of the Anti-Obesity Medication Phentermine (Leap) Trial: Rationale, Design, and Baseline Characteristics

Authors

• Caroline Blackwell Young
• Emily Rives
• Kimberly A Gudzune
• Byron C Jaeger
• Courtney G Simmons
• Brian N White
• Stephanie A Hooker
• Deborah B Horn
• Deborah R Young
• Jennifer Vesely
• Amanda Velazquez
• Catherine Price
• Shelly D Cook
• Katy Martin-Fernandez
• Galina Inzhakova
• Nicholas M Pajewski
• Jamy D Ard
• Kristina H Lewis

Language

English

Publication Date

2-1-2026

Journal

Contemporary Clinical Trials

DOI

10.1016/j.cct.2026.108219

PMID

41519431

PMCID

PMC12973477

PubMedCentral® Posted Date

3-11-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Background: Current clinical practice guidelines support the long-term use of pharmacotherapy for obesity treatment. Historically, phentermine has been one of the most prescribed obesity medications (OMs), however, its long-term efficacy and safety have never been evaluated in a randomized trial as its market approval predates such requirements. Here we describe the design, rationale, and baseline characteristics for a 24-month, double-blind, randomized controlled trial evaluating the efficacy, cardiovascular risk, and safety of phentermine in adults with overweight or obesity.

Methods: This multicenter trial will compare outcomes among participants randomized to phentermine 24 mg daily versus placebo for 24 months. All participants also receive an online lifestyle intervention. A total of 870 participants with body mass index of 27-44.9 kg/m2 were randomized across six sites in North Carolina (2), Minnesota, Texas, and California (2). Primary outcomes are 24-month mean percent weight loss (efficacy), 24-month mean change in systolic blood pressure (cardiometabolic risk), and overall rates of adverse events and serious adverse events (safety). Secondary outcomes include changes in resting energy expenditure/resting metabolic rate, cardiac autonomic function measured using heart rate variability with electrocardiogram, and a self-reported measure of phentermine dependence.

Conclusions: The safety and efficacy of long-term phentermine remains a pressing, unanswered question, particularly given its low cost and high availability when compared to newer OMs that are highly effective but often associated with significant costs. This study will impact clinical practice regardless of result - either providing evidence to support use of an available low-cost option or prioritizing the use of other OMs.

Keywords

Humans, Phentermine, Obesity, Double-Blind Method, Anti-Obesity Agents, Female, Weight Loss, Adult, Blood Pressure, Multicenter Studies as Topic, Randomized Controlled Trials as Topic, Body Mass Index, Male, Middle Aged, Overweight, Obesity Medications, Obesity, Adult, Randomized Controlled Trial

Comments

Trial registration: Clinicaltrials.gov, NCT05176626.

Published Open-Access

yes

Recommended Citation

Young, Caroline Blackwell; Rives, Emily; Gudzune, Kimberly A; et al., "The Long-Term Effectiveness of the Anti-Obesity Medication Phentermine (Leap) Trial: Rationale, Design, and Baseline Characteristics" (2026). Faculty, Staff and Student Publications. 4512.
https://digitalcommons.library.tmc.edu/uthmed_docs/4512