ObesityPhase 2NCT05933499
Effect of Tirzepatide and Bimagrumab on Body Composition, Insulin Sensitivity, and Bone in Adults With Obesity
A Phase 2 study testing Bimagrumab, Tirzepatide and Calcium/Vitamin D in people with Obesity, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
In adults with obesity seeking treatment, weight loss would ideally be composed almost exclusively of fat mass. However, loss of muscle mass and bone are unintentional consequences of weight loss, which may have negative effects on health by lessening improvements in glucose and insulin levels, reducing resting… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Obesity
- What is being tested?
- Bimagrumab, Tirzepatide and Calcium/Vitamin D
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Nov 2025to 31 Mar 2029
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- BMI ≥30 kg/m2 or ≥27kg/m2 with at least one weight-related medical condition
- Have a history of at least one self-reported unsuccessful behavioral effort to lose body weight
- Have an established primary care provider
Who cannot join
- Current or prior history of diabetes mellitus based on self-report, use of diabetes medications, HbA1c ≥6.5%, or fasting glucose ≥126 mg/dL
- Any single serum transaminase level (i.e., ALT, AST, alk phos) ≥3x the upper limit of normal (ULN)
- Serum lipase and/or amylase levels ≥2x ULN
- Serum bilirubin level >1.6 mg/dL
- Chronic kidney disease (e.g., estimated glomerular filtration rate (eGFR) < 45 mL/min)
- Total WBC <3000/μL, neutrophils <1500/μL, hemoglobin <12 g/dL, or platelet count <100,000/μL
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- Significant coagulopathy, e.g., PT/INR >1.5
- History of familial hypertriglyceridemia or serum fasting triglyceride >500 mg/dL
- Uncontrolled thyroid disease, defined as abnormal TSH with abnormal fT4
- Any chronic active infection (e.g., HIV, hepatitis B or C) or hepatitis C treatment within the previous 6 months
- Known history or presence of severe active acute or chronic liver disease (e.g., cirrhosis) or conditions with hepatotoxic potential (e.g., gallbladder or bile duct disease, acute or chronic pancreatitis, exocrine pancreatic insufficiency)
- Active clinically significant gastric emptying abnormality or chronic use of a drug(s) that directly affect GI motility
- History of calcium oxalate kidney stones
- History of clinically significant arrhythmias, unstable angina, myocardial infarction, stroke, coronary artery bypass graft surgery, percutaneous coronary intervention, heart failure, valve disorders or defect, pulmonary hypertension, chronic hypotension (<100/50), or chronic uncontrolled hypertension (>160/100)
- Tachycardia, defined as heart rate >100 bpm after 5 minutes resting in a sitting position
- History of malignancy of any organ system (other than localized squamous or basal cell carcinoma of the skin), treated or untreated, within the previous 5 years
- Confirmed diagnosis of current, significant psychiatric disease (e.g., dementia, Alzheimer's disease, schizophrenia, or bipolar disorder). Individuals with adequately treated depression on stable treatment for at least 3 months are eligible.
- Prior history of suicide attempt
- PHQ-9 score ≥ 15 at screening
- Personal or family history of multiple endocrine neoplasia 2A or 2B or medullary thyroid cancer
- Active alcohol, drug, or tobacco abuse. For alcohol, an average weekly alcohol intake that exceeds 14 units per week (males) or 7 units per week (females) [1 unit = 12 oz or 260 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits] is exclusionary.
- Cannabis/THC use greater than once a week over the past three months and unwilling to abstain from use of cannabis/THC products for the duration of the study
- Have obesity induced by other endocrinologic disorders (e.g., Cushing syndrome) or diagnosed monogenetic or syndromic forms of obesity (e.g., Melanocortin 4 Receptor deficiency or Prader Willi syndrome)
- History of weight loss surgery or planned weight loss surgery during the trial period
- Use of any anti-obesity medication, nutritional supplement, or over the counter (OTC) product for weight loss within the previous 6 months or during study participation
- Any new dietary intervention or exercise regimen for weight loss started within the previous 3 months
- Weight instability of >5kg within the previous 3 months
- Weight > 150kg due to limitations of radiology imaging machines
- Use of medications known or suspected to induce weight gain within the previous 3 months or during study participation (e.g., anti-androgens, gonadotropin releasing hormone (GnRH) analogs, some anticonvulsant and psychotropic medications (excluding anti-depressant medication) and oral glucocorticoids)
- Use of skeletal muscle anabolic agents within the previous 3 months or during study participation (e.g., hormones such as growth hormone or testosterone, nutritional supplements (other than protein) and over-the-counter products labeled as muscle anabolic agents)
- Treatment with glucose-lowering agent(s) within 90 days before screening
- History of hypersensitivity to monoclonal antibodies or drugs in the same compound class as the study drugs
- History of fragility fracture or BMD T-score ≤ -2.5 in participants > 50 years old
- Use of IV bisphosphonates within the previous 2 years or other osteoporosis medications within the previous 12 months or during study participation
- Not able or willing to comply with dietary and lifestyle intervention for weight loss, including history of clinically significant condition that precludes regular walking for exercise or contraindication to following a 500-calorie daily deficit, high protein diet
- Women who are pregnant or breastfeeding
- Women of child-bearing potential, defined as women physiologically capable of becoming pregnant, unless they are using an intrauterine device (IUD) from at least 3 months before the baseline visit through at least 4 months after the last drug dose and an additional contraceptive (barrier) method from screening through at least 4 months after the last drug dose. Women not of child-bearing potential are defined as individuals who (1) have a congenital anomaly such as Mullerian agenesis, resulting in confirmed infertility, (2) are infertile due to surgical sterilization (defined as documented hysterectomy, bilateral salpingo-oophorectomy, bilateral salpingectomy, or bilateral oophorectomy), or (3) are post-menopausal. The following groups of women are eligible to participate: (a) women who are s/p surgical bilateral oophorectomy or total hysterectomy at least 6 weeks before taking study treatment, (b) women who have an IUD (see additional criteria above), (c) women who are s/p tubal ligation provided that they use an additional barrier form of contraception from screening through at least 4 months after the last drug dose, (d) women who are post-menopausal defined as ≥12 months of spontaneous amenorrhea with appropriate clinical and hormonal profile (e.g., age-appropriate, history of vasomotor symptoms, and/or FSH >40 IU/L), (e) have a congenital anomaly resulting in confirmed infertility, and (f) do not have a history of sexual activity that could lead to pregnancy (i.e., total abstinence has been and is their preferred lifestyle or same-sex partners only).
- For men, morning serum testosterone less than 200 ng/dL
- Concurrently enrolled in any other type of medical research judged to be scientifically or medically incompatible with this study
- Plans to move out of the study area within 16 months, or be out of the study area for >4 weeks, continuously
- Routine MRI exclusion
- Donation or loss of 400 mL or more of blood within past 2 months or plasma donation (> 250 mL) within past 2 weeks
- Major surgery in the trial period
- Any disorder, unwillingness, or inability not covered by any of the other exclusion criteria, which in the Investigator's opinion, might jeopardize the subject's safety or compliance with the protocol
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, 1 recruiting
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Melanie Haines, MD, 617-726-3870, mshaines@mgh.harvard.edu
About this study
In adults with obesity seeking treatment, weight loss would ideally be composed almost exclusively of fat mass. However, loss of muscle mass and bone are unintentional consequences of weight loss, which may have negative effects on health by lessening improvements in glucose and insulin levels, reducing resting metabolic rate, and increasing the risk of falls and fractures. Data in animals and humans suggest that bimagrumab, an investigational new drug for obesity that inhibits the activin type II receptor (ActRII) inhibitor, may help maximize loss of fat mass while maintaining muscle mass when used in combination with a glucagon-like peptide 1 receptor agonist (GLP-1 RA). The investigators hypothesize that in a randomized, placebo-controlled trial of 63 adults with obesity randomized to tirzepatide (GLP-1/GIP RA) + bimagrumab, tirzepatide alone, or bimagrumab alone, the combination of tirzepatide + bimagrumab will result in improvements in muscle, fat, and bone compared to tirzepatide alone or bimagrumab alone when given in addition to a lifestyle intervention for weight loss over 52 weeks.
- Conditions
- Obesity
- Being tested
- Bimagrumab, Tirzepatide, Calcium/Vitamin D, Lifestyle and nutrition counseling
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BimagrumabDrug
SQ bimagrumab 300mg qweek
TirzepatideDrug
SQ tirzepatide 15mg qweek
Calcium/Vitamin DDietary supplement
Elemental calcium 1200 mg + vitamin D3 800 IU PO daily
Lifestyle and nutrition counselingBehavioural
Lifestyle and nutrition counseling consistent with current guidelines for weight management
| Study group | Role | What they receive |
|---|---|---|
| Tirzepatide + bimagrumab | Experimental | Not described Receives: Drug: Bimagrumab; Drug: Tirzepatide; Dietary Supplement: Calcium/Vitamin D; Behavioral: Lifestyle and nutrition counseling |
| Tirzepatide + placebo | Active comparator | Not described Receives: Drug: Tirzepatide; Dietary Supplement: Calcium/Vitamin D; Behavioral: Lifestyle and nutrition counseling |
| Bimagrumab + placebo | Active comparator | Not described Receives: Drug: Bimagrumab; Dietary Supplement: Calcium/Vitamin D; Behavioral: Lifestyle and nutrition counseling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in number of kilograms of lean mass by dual-energy x-ray absorptiometry
Change in number of kilograms of lean mass by dual-energy x-ray absorptiometry in tirzepatide + bimagrumab vs. tirzepatide groups
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2023
- Study start5 Nov 2025
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Mar 2029 (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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 63 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Melanie Schorr Haines, M.D, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05933499
- Sponsor's protocol ID
- 2023P001334
- Status last verified
- Mar 2026
- First submitted
- 27 Jun 2023
- Last updated
- 27 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Tirzepatide and Bimagrumab on Body Composition, Insulin Sensitivity, and Bone in Adults With Obesity
- ClinicalTrials.gov ID
- NCT05933499
- Acronym / sponsor ID
- 2023P001334
- Conditions
- Obesity
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 63 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- 5 Nov 2025 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 31 Mar 2029 (estimated)
- First posted
- 6 Jul 2023 (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.
In adults with obesity seeking treatment, weight loss would ideally be composed almost exclusively of fat mass. However, loss of muscle mass and bone are unintentional consequences of weight loss, which may have negative effects on health by lessening improvements in glucose and insulin levels, reducing resting metabolic rate, and increasing the risk of falls and fractures. Data in animals and humans suggest that bimagrumab, an investigational new drug for obesity that inhibits the activin type II receptor (ActRII) inhibitor, may help maximize loss of fat mass while maintaining muscle mass when used in combination with a glucagon-like peptide 1 receptor agonist (GLP-1 RA). The investigators hypothesize that in a randomized, placebo-controlled trial of 63 adults with obesity randomized to tirzepatide (GLP-1/GIP RA) + bimagrumab, tirzepatide alone, or bimagrumab alone, the combination of tirzepatide + bimagrumab will result in improvements in muscle, fat, and bone compared to tirzepatide alone or bimagrumab alone when given in addition to a lifestyle intervention for weight loss over 52 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Tirzepatide + bimagrumab | Experimental | Drug: Bimagrumab, Drug: Tirzepatide, Dietary Supplement: Calcium/Vitamin D, Behavioral: Lifestyle and nutrition counseling |
| Tirzepatide + placebo | Active comparator | Drug: Tirzepatide, Dietary Supplement: Calcium/Vitamin D, Behavioral: Lifestyle and nutrition counseling |
| Bimagrumab + placebo | Active comparator | Drug: Bimagrumab, Dietary Supplement: Calcium/Vitamin D, Behavioral: Lifestyle and nutrition counseling |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- BMI ≥30 kg/m2 or ≥27kg/m2 with at least one weight-related medical condition
- Have a history of at least one self-reported unsuccessful behavioral effort to lose body weight
- Have an established primary care provider
Key exclusion criteria (44 listed)
- Current or prior history of diabetes mellitus based on self-report, use of diabetes medications, HbA1c ≥6.5%, or fasting glucose ≥126 mg/dL
- Any single serum transaminase level (i.e., ALT, AST, alk phos) ≥3x the upper limit of normal (ULN)
- Serum lipase and/or amylase levels ≥2x ULN
- Serum bilirubin level >1.6 mg/dL
- Chronic kidney disease (e.g., estimated glomerular filtration rate (eGFR) < 45 mL/min)
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 |
|---|---|---|
| BimagrumabSQ bimagrumab 300mg qweek | Drug | Bimagrumab + placebo, Tirzepatide + bimagrumab |
| TirzepatideSQ tirzepatide 15mg qweek | Drug | Tirzepatide + bimagrumab, Tirzepatide + placebo |
| Calcium/Vitamin DElemental calcium 1200 mg + vitamin D3 800 IU PO daily | Dietary supplement | Bimagrumab + placebo, Tirzepatide + bimagrumab, Tirzepatide + placebo |
| Lifestyle and nutrition counselingLifestyle and nutrition counseling consistent with current guidelines for weight management | Behavioural | Bimagrumab + placebo, Tirzepatide + bimagrumab, Tirzepatide + placebo |
Primary outcome
Change in number of kilograms of lean mass by dual-energy x-ray absorptiometry
Time frame: 52 weeks
Change in number of kilograms of lean mass by dual-energy x-ray absorptiometry in tirzepatide + bimagrumab vs. tirzepatide groups
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 Mar 2026.
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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 2 study testing Bimagrumab, Tirzepatide and Calcium/Vitamin D 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 3 inclusion and 44 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: looking for participants now, as of the sponsor's last update on 27 Mar 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Melanie S Haines, MD (617-726-3870, mshaines@mgh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in number of kilograms of lean mass by dual-energy x-ray absorptiometry (time frame: 52 weeks). 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 Mar 2026.