ObesityPhase 4NCT07729332
Switching to Oral Weight Management Pharmacotherapy to Prevent Weight Regain After GLP-1 Therapy Discontinuation
A Phase 4 study testing Phentermine Pill and Orforglipron in people with Obesity, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
This study will compare the effect of orforglipron and phentermine on weight maintenance. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Obesity
- What is being tested?
- Phentermine Pill and Orforglipron
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2026to 31 Jul 2031
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 27Show fewer
- 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
- Known contraindications to phentermine:
- History of coronary artery, cerebrovascular or peripheral arterial disease including myocardial infarction, unstable angina, revascularization, stroke/TIA, carotid intervention, claudication
- Poorly-controlled blood pressure (>149/94) or elevated heart rate (>110 bpm)
- History of cardiac arrhythmia
- History of valvular heart disease
- Congestive heart failure (any history or current)
- Active / currently-treated hyperthyroidism (thyroid function screening required if pulse>100)
- History of glaucoma or been told by an ophthalmologist that you are at high risk for glaucoma
- 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)
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: Switching to Oral Weight Management Pharmacotherapy to Prevent Weight Regain After GLP-1-based Therapy Discontinuation
This study will compare the effect of orforglipron and phentermine on weight maintenance.
- Conditions
- Obesity
- Being tested
- Phentermine Pill, Orforglipron
- Keywords
- weight maintenance
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Phentermine PillDrug
Phentermine 8 mg or 37.5 mg tablet
OrforglipronDrug
orforglipron 0.8, 2.5, 5.5, 9, 14.5 or 17.2 mg tablets
| Study group | Role | What they receive |
|---|---|---|
| Phentermine | Active comparator | Phentermine Receives: Drug: Phentermine Pill |
| Orforglipron | Active comparator | Orforglipron Receives: Drug: Orforglipron |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent change in body weight
Percent change in body weight from randomization to 6 months
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2026
- Study start1 Nov 2026 (estimated)
- Primary completion31 Jul 2031 (estimated)
- Study completion31 Jul 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Deborah Wexler, MD, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07729332
- Sponsor's protocol ID
- R01DK148554
- Status last verified
- Jul 2026
- First submitted
- 22 Jul 2026
- Last updated
- 27 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: It will be shared; data sharing plan is under review; will update when approved.
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Switching to Oral Weight Management Pharmacotherapy to Prevent Weight Regain After GLP-1-based Therapy Discontinuation
- ClinicalTrials.gov ID
- NCT07729332
- Acronym / sponsor ID
- R01DK148554
- Conditions
- Obesity
- Keywords
- weight maintenance
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- 1 Nov 2026 (estimated)
- Primary completion
- 31 Jul 2031 (estimated)
- Study completion
- 31 Jul 2031 (estimated)
- First posted
- 27 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will compare the effect of orforglipron and phentermine on weight maintenance.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phentermine | Active comparator | Drug: Phentermine PillPhentermine |
| Orforglipron | Active comparator | Drug: OrforglipronOrforglipron |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (27 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Phentermine PillPhentermine 8 mg or 37.5 mg tablet | Drug | Phentermine |
| Orforglipronorforglipron 0.8, 2.5, 5.5, 9, 14.5 or 17.2 mg tablets | Drug | Orforglipron |
Primary outcome
Percent change in body weight
Time frame: 6 months
Percent change in body weight from randomization to 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2026.
- Individual participant dataSharing planned: Undecided. It will be shared; data sharing plan is under review; will update when approved.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Phentermine Pill and Orforglipron in people with Obesity, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 27 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Deborah J Wexler, MD (617-726-8767, dwexler@mgh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent change in body weight (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2026.