Oral pills may help keep weight off after stopping popular injections
NCT ID NCT07729332
First seen Jul 27, 2026 · Last updated Jul 28, 2026 · Updated 1 time
Summary
This study tests whether switching to an oral weight-loss medication—either phentermine or orforglipron—can help people maintain weight loss after they stop taking injectable GLP-1 drugs like semaglutide or tirzepatide. Participants must have lost at least 10% of their body weight on the injectable therapy. The trial will compare the two oral options over six months to see which better prevents weight regain.
What this could mean
Our plain-language read of the trial. This is informational only, not medical advice or a prediction.
- Active substance
- phentermine or orforglipron oral tablets
- What this could lead to
- If successful, this could offer a practical way to maintain weight loss after stopping popular injectable GLP-1 drugs, reducing the need for lifelong injections.
- What could go wrong
- This is a small, early-phase trial with only 60 participants, so results may not apply broadly. Both phentermine and orforglipron have side effects, and weight regain may still occur.
This is an AI summary of the original study and may miss details. Read our disclaimer.
Study facts
What this study's own registry entry says, in plain language.
- Phase
-
Phase 4
Runs after approval, following long-term safety and how well the treatment works in everyday use.
- Participants
-
About 60 people
The number the study aims to enrol. It can still change while the study runs.
- Expected to start
-
Nov 2026
An estimate. Start dates often move.
- Expected to finish
-
Jul 2031
An estimate. End dates often move.
- Lead sponsor
-
Other sponsor
The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.
Who can take part
This study's own entry requirements. Only the study team can say for certain whether you qualify.
- Ages
-
18 to 80 years
- Sex
-
Anyone
- Healthy volunteers
-
Not accepted
This study is not open to healthy volunteers. The entry requirements below say who it is open to.
Show the full entry requirements Hide the full entry requirements
Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.
Inclusion Criteria: 1. Age 18-80 years at screening 2. History of BMI ≥30 kg/m² 3. Current or recent (within 8 weeks) treatment with injectable semaglutide, tirzepatide, or similar GLP-1 based medication 4. Achieved ≥10% body weight loss since initiation of injectable semaglutide, tirzepatide or similar GLP-1 based medication 5. Willing to participate in the study after reviewing study infographic and confirming understanding of randomization and study procedures 6. Ability to understand and the willingness to sign a written informed consent document 7. Residence in Massachusetts Exclusion Criteria: 1. Current type 2 diabetes mellitus 2. Recent or planned surgical obesity treatment (bariatric surgery \>1 year prior to GLP-1 initiation allowed) 3. Pregnancy, intent to become pregnant, or current breastfeeding (participants of childbearing potential must have a negative pregnancy test at baseline) 4. History of pancreatitis 5. History of transplanted organ (corneal transplants permitted) or awaiting organ transplant 6. Obesity induced by endocrinologic disorders (e.g., Cushing syndrome) or diagnosed monogenic/syndromic obesity (e.g., MC4R deficiency, Prader-Willi syndrome) 7. 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 8. Any history of a suicide attempt 9. Systemic glucocorticoid therapy \>2 weeks within the prior 3 months, or anticipated need within the next 12 months 10. Use of medications known to cause significant weight gain (e.g., olanzapine, lithium) within the last 3 months. 11. Quit using nicotine-containing products less than 6 months prior to baseline visit or intention to quit use in the next year 12. Current use strong CYP3A4 inducer medications (which may include: phenytoin, carbamazepine, phenobarbital, primidone, lumacaftor, midostaurin, and pentobarbital). 13. 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 14. Chronic kidney disease stage 3b or lower (eGFR \<45 mL/min/1.73m²) 15. Acute hepatitis or liver failure/cirrhosis 16. Known contraindications to phentermine: 1. History of coronary artery, cerebrovascular or peripheral arterial disease including myocardial infarction, unstable angina, revascularization, stroke/TIA, carotid intervention, claudication 2. Poorly-controlled blood pressure (\>149/94) or elevated heart rate (\>110 bpm) 3. History of cardiac arrhythmia 4. History of valvular heart disease 5. Congestive heart failure (any history or current) 6. Active / currently-treated hyperthyroidism (thyroid function screening required if pulse\>100) 7. History of glaucoma or been told by an ophthalmologist that you are at high risk for glaucoma 8. Heavy alcohol use within the last 6 months (men: more than 4 drinks on any day or more than 14 drinks per week; women: more than 3 drinks on any day or more than 7 drinks per week) 9. History of substance use disorder or active use of illicit substances within the last 12 months. Tetrahydrocannabinol (THC)-containing products will not be considered an illicit substance. (e.g., uncontrolled hypertension, active/unstable cardiovascular disease, arrhythmia, hyperthyroidism \[thyroid function screening required if pulse\>100\], glaucoma, history of substance use disorder 16\. Use of any stimulant medications. 17. Known contraindication to orforglipron (e.g., personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2). 18\. Any condition (e.g., drug or alcohol abuse, diagnosed eating disorder, other psychiatric disorder) that in the investigator's opinion may preclude protocol compliance
Get updates
Get notified about this study
Sign up to get updates when this study changes or when new studies for Obesity are added.
Genom att skicka in godkänner du våra Användarvillkor
Conditions
The condition(s) this trial relates to.
As listed by the trial registrant
The condition terms exactly as the trial's registrant entered them.
How to take part
Only the study team decides who joins. These are the ways to reach them.
-
The places running it
1 site. The list below names each one and where it is.
-
The official record
ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.
-
A doctor treating you
A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.
Contacts and locations
Locations
-
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
More trials for these conditions
Other studies related to the condition(s) this trial covers.
- Custom knee guides put to the test in obese patients
- A pill for obesity? early human trial puts MDR-001 to the test
- Can a weekly shot help people who still struggle with weight after bariatric surgery?
- Do GLP-1 Weight-Loss drugs change how teens eat and feel?
- Can electrical muscle stimulation boost exercise benefits after menopause?
- Can a cold cloth on the neck calm Post-Surgery nausea?