Switching to Oral Weight Management Pharmacotherapy to Prevent Weight Regain After GLP-1 Therapy Discontinuation
Switching to Oral Weight Management Pharmacotherapy to Prevent Weight Regain After GLP-1-based Therapy Discontinuation
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years to 80 Years
- Sex
- All sexes
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
Not stated in the study description — ask the study team about visits and procedures.
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This study compares two weight-loss pills, orforglipron and phentermine, to help prevent weight regain after stopping GLP-1 shots. It is for adults in Massachusetts who have lost at least 10% of their body weight while using these shots.
This study will compare the effect of orforglipron and phentermine on weight maintenance.
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- You are 18–80 years old.
- You have had a BMI of 30 or higher. BMI is a measure based on height and weight.
- You use semaglutide, tirzepatide, or a similar GLP-1 shot now, or used one within the past 8 weeks.
- You have lost at least 10% of your body weight since starting these shots.
- You are willing to join after reviewing the study guide and understanding the steps and how treatment is assigned by chance.
- You can understand and are willing to sign a consent form.
- You live in Massachusetts.
Who can't join
- You have type 2 diabetes, past inflammation of the pancreas, serious kidney disease (eGFR below 45), sudden liver inflammation, liver failure, or liver scarring.
- You have had recent weight-loss surgery or plan to have it. Surgery more than 1 year before starting GLP-1 treatment is allowed. You have had or are waiting for an organ transplant, except a cornea transplant.
- You are pregnant, plan to become pregnant, or are breastfeeding. Anyone who could become pregnant must have a negative pregnancy test at the first study visit.
- Your obesity is caused by a hormone disorder or certain genetic conditions. You have a personal or family history of medullary thyroid cancer or MEN2, an inherited condition that can cause tumors.
- You have had serious active or unstable depression or another severe mental health condition in the past 2 years, or have ever attempted suicide. Other conditions that could prevent you from following study steps may also rule you out.
- You use stimulant medicines or certain medicines that change how the body handles drugs. Other limits apply to steroid treatment, medicines that cause major weight gain, and weight-loss medicines other than GLP-1 shots.
- You have certain heart or blood vessel diseases, an irregular heartbeat, heart valve disease, heart failure, blood pressure above 149/94, or a pulse above 110. An active or treated overactive thyroid, glaucoma, or high risk for glaucoma also rules you out.
- You quit nicotine less than 6 months ago or plan to quit in the next year. Heavy drinking in the past 6 months, a history of substance use disorder, or illegal drug use in the past year also rules you out; THC products do not count as illegal drugs in this study.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
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
Study sites (1)
MA
- Massachusetts General Hospital · Boston, MA 02114More trials in Boston