Switching to Oral Weight Management Pharmacotherapy to Prevent Weight Regain After GLP-1 Therapy Discontinuation

NCT07729332 | Not Yet Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: R01DK148554
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This study will compare the effect of orforglipron and phentermine on weight maintenance.

Conditions

Obesity

Keywords

weight maintenance

Outcome Measures

Primary Outcomes (1)

• Percent change in body weight

  Percent change in body weight from randomization to 6 months

  6 months

Study Arms (2)

Phentermine

ACTIVE COMPARATOR

Phentermine

Drug: Phentermine Pill

Orforglipron

ACTIVE COMPARATOR

Orforglipron

Drug: Orforglipron

Interventions

Phentermine Pill DRUG

Phentermine 8 mg or 37.5 mg tablet

Phentermine

Orforglipron DRUG

orforglipron 0.8, 2.5, 5.5, 9, 14.5 or 17.2 mg tablets

Orforglipron

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-80 years at screening
• History of BMI ≥30 kg/m²
• Current or recent (within 8 weeks) treatment with injectable semaglutide, tirzepatide, or similar GLP-1 based medication
• Achieved ≥10% body weight loss since initiation of injectable semaglutide, tirzepatide or similar GLP-1 based medication
• Willing to participate in the study after reviewing study infographic and confirming understanding of randomization and study procedures
• Ability to understand and the willingness to sign a written informed consent document
• Residence in Massachusetts

You may not qualify if:

• Current type 2 diabetes mellitus
• Recent or planned surgical obesity treatment (bariatric surgery \>1 year prior to GLP-1 initiation allowed)
• Pregnancy, intent to become pregnant, or current breastfeeding (participants of childbearing potential must have a negative pregnancy test at baseline)
• History of pancreatitis
• History of transplanted organ (corneal transplants permitted) or awaiting organ transplant
• Obesity induced by endocrinologic disorders (e.g., Cushing syndrome) or diagnosed monogenic/syndromic obesity (e.g., MC4R deficiency, Prader-Willi syndrome)
• History of significant active or unstable major depressive disorder or other severe psychiatric disorder (e.g., schizophrenia, bipolar disorder, serious mood or anxiety disorder) within the past 2 years
• Any history of a suicide attempt
• Systemic glucocorticoid therapy \>2 weeks within the prior 3 months, or anticipated need within the next 12 months
• Use of medications known to cause significant weight gain (e.g., olanzapine, lithium) within the last 3 months.
• Quit using nicotine-containing products less than 6 months prior to baseline visit or intention to quit use in the next year
• Current use strong CYP3A4 inducer medications (which may include: phenytoin, carbamazepine, phenobarbital, primidone, lumacaftor, midostaurin, and pentobarbital).
• Use of prescription or over-the-counter weight loss medications within the last 3 months, other than semaglutide, tirzepatide, or other injectable GLP-1 medication
• Chronic kidney disease stage 3b or lower (eGFR \<45 mL/min/1.73m²)
• Acute hepatitis or liver failure/cirrhosis

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Obesity

Interventions

Phentermine; orforglipron

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Central Study Contacts

Deborah J Wexler, MD

CONTACT

617-726-8767; dwexler@mgh.harvard.edu

Sarah Kanbour, MD

CONTACT

617-726-8767; skanbour@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine, Harvard Medical School

Study Record Dates

• First Submitted: July 22, 2026
• First Posted: July 27, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): July 31, 2031
• Study Completion (Estimated): July 31, 2031
• Last Updated: July 27, 2026

Record last verified: 2026-07

Locations

US (1)