Sequential or CombinaTion Anti-obesitY Medication With Muscle Preservation for Weight Loss and MaintEnance: A PragmAtic Randomized CoNtrolled Trial (STAY-LEAN Trial)

NCT06854614 · Active, not recruiting

Last updated 2026-05-28

This clinical trial is testing whether combining anti-obesity medications or using them one after another helps people with obesity lose and maintain weight better.

Status Active, not recruiting Ongoing, but no longer enrolling new participants.

Phase Phase 4 Monitors a drug already on the market.

Type Interventional (clinical trial)

Design Randomized, open-label (no blinding) treatment study

Participants 150 people

Who can join Ages 25–65 · all sexes

Timeline Started 2025-03 · est. completion 2028-04

Where 1 site · United States

What this study is testing ClinicalTrials.gov NCT06854614 ↗

Description as written by the study sponsor.

This is a prospective, pragmatic, 21 month, single-center, randomized, 2-phased, open-label, parallel-group trial comparing the use of enhanced lifestyle changes (ELC) in two different sequential anti obesity medication (AOM) therapies. The ELC consists of a medically-supervised and comprehensive weight loss program (Cleveland Clinic's Department of Endocrinology, Diabetes and Metabolism's Integrated Weight Management Program). In the first phase (9 months) of the study, all participants will receive tirzepatide 15 mg (option #1) or semaglutide 2.4 mg if tirzepatide is not tolerated. In the second phase, after completing 9 months of tirzpeatide or semaglutide, participants will continue ELC and will be randomly assigned to a different oral AOM therapy for another 12 months: group 1 (phentermine-topiramate or naltrexone-bupropion) or group 2 (orlistat). The primary endpoint will be the percentage weight loss at 21 months compared to weight loss at 9 months. The goal will be to show superiority of the arm receiving ELC plus AOM therapy (phentermine-topiramate or naltrexone-bupropion) when compared to the other AOM therapy group (orlistat). Secondary and exploratory endpoints will include percentage of fat mass loss, lean muscle mass, functional capacity, muscle strength and compliance to enhanced lifestyle changes. Informed consent will be obtained. IRB approval of the study will be obtained.

Treatments tested

Comprehensive weight loss Other

Shared Medical Appointments
Enhanced lifestyle changes Other

Subjects will also be referred to an exercise physiologist for a personalized physical activity program. Physical Activity and Exercise will be discussed during SMAs as well and individually as needed for exercise progression The participants exercise prescription will be individualized based on an initial assessment. Exercise duration and progression will be recommended at the discretion of staff and exercise physiologist. The exercise program will be structured but flexible, which means patients can substitute group exercises with individual exercise if necessary, following the FITT-VP format (frequency, intensity, time, type, volume and progression). Patients can reduce exercise frequency if the duration is prolonged, or intensity is increased. Investigators will encourage patients to use Cleveland Clinic gyms across the enterprise.
Phentermine-Topiramate also known as Qsymia Drug

Medication for chronic weight management (Rx)
Naltrexone-Bupropion Combination also known as Contrave Drug

Medication for chronic weight management (Rx)
Orlistat also known as Xenical Drug

Medication for chronic weight management (Rx)

Main thing measured	Weight change
Sponsor	The Cleveland Clinic
Conditions studied	Obesity
GLP-1 drugs	—

Full protocol, eligibility, and contacts on ClinicalTrials.gov NCT06854614 ↗