Tirzepatide + Lifestyle Changes for Obesity

(GRAMS Trial)

Overseen By Seaneen Hebert, MS

Age: 18 - 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Pennington Biomedical Research Center

Must be taking: GLP-1 therapy

Must not be taking: Corticosteroids, Osteoporosis therapies

Disqualifiers: Menopausal, Osteoporosis, Diabetes, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 5 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effects of Tirzepatide, a medication, combined with lifestyle changes like diet and exercise for weight loss. Researchers aim to understand how these treatments might impact muscles and bones in individuals who lose weight. Participants will be divided into two groups: one will use Tirzepatide with a special lifestyle plan, and the other will use Tirzepatide with regular diet and exercise. The trial seeks individuals with a BMI (a measure of body fat) between 30 and 40 who can adhere to the provided lifestyle plan. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to the potential availability of a new weight loss treatment.

Will I have to stop taking my current medications?

Yes, if you are on medications that affect weight or are systemic corticosteroids, you will need to stop taking them to participate in this trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that tirzepatide is generally safe for weight loss. In studies, individuals without diabetes who took tirzepatide experienced significant weight loss. However, some safety concerns exist. A review found that while tirzepatide helped reduce body fat, some participants reported side effects. Although real-world data on its safety remains limited, some negative effects have been noted post-marketing. Anyone considering joining the trial should consider these findings and discuss any concerns with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for obesity?

Tirzepatide is unique because it targets both GLP-1 and GIP receptors, unlike most obesity treatments that focus only on GLP-1. This dual-action approach may enhance weight loss and improve metabolic health more effectively. Researchers are excited about tirzepatide because it could offer a more comprehensive solution for obesity by not only reducing weight but also potentially improving insulin sensitivity and other related metabolic markers.

What evidence suggests that Tirzepatide might be an effective treatment for obesity?

Research has shown that tirzepatide aids in weight loss. Studies found that individuals taking tirzepatide lost significantly more weight than those taking semaglutide, with an average difference of 6.5 percentage points. In one study, participants on tirzepatide lost 10% or more of their starting weight after 72 weeks. Another study demonstrated that people using tirzepatide for six months lost an average of 12.9% of their body weight. In this trial, participants in the treatment group will receive tirzepatide along with a lifestyle toolkit, while those in the control group will receive tirzepatide with regular diet and exercise. These findings suggest that tirzepatide can be a strong option for reducing obesity. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with osteoporosis, musculoskeletal disorders, or obesity who are not suitable candidates for current osteoporosis prevention drugs. It's also aimed at those experiencing muscle loss and fat gain.

Inclusion Criteria

Rural males and females will be enrolled at MaineHealth

Females have had their last menstrual period less than 60 days before screening

My BMI is between 30 and 40.

Exclusion Criteria

Injectable contraceptives such as Depo-Provera are a cause for exclusion

Fertility Appreciation Based Methods (natural family planning) are also acceptable forms of addressing childbearing potential in all subjects. A urine pregnancy test (UPT) will be performed on all females of childbearing potential at the screening visit, 3 and 6 months

Patient Health Questionnaire-9 (PHQ-9) Score equal to or greater than 15 (clinical depression)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive treatment with Tirzepatide and a lifestyle toolkit or regular diet and exercise for 5 months

5 months

Visits at baseline, 3 months, and 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lifestyle toolkit
• Tirzepatide

Trial Overview The GRAMS study is testing the effects of a drug called Tirzepatide on weight loss and musculoskeletal health compared to a control group following regular diet and exercise routines. Participants will also receive a lifestyle toolkit to assist in their weight management.

How Is the Trial Designed?

Group I: Treatment/intervention group Experimental Treatment 1 Intervention

Treatment with Tirzepatide for 5 months and lifestyle toolkit.

Group II: Control/Placebo Placebo Group 1 Intervention

Treatment with Tirzepatide for 5 months with regular diet and exercise.

Who Is Running the Clinical Trial?

Pennington Biomedical Research Center

Lead Sponsor

Trials

314

Recruited

183,000+

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2416394

Tirzepatide as Compared with Semaglutide for ... Tirzepatide was superior to semaglutide with respect to weight reduction (estimated treatment difference, −6.5 percentage points; 95% CI, −8.1 ...

2. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2812936

Continued Treatment With Tirzepatide for Maintenance of ... From randomization (at week 36), those switched to placebo experienced a 14% weight regain and those continuing tirzepatide experienced an ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12326891/

Weight reduction over time in tirzepatide‐treated ... A weight reduction of 5% or more is typically needed to improve or prevent some of the complications of obesity, such as type 2 diabetes, dyslipidaemia, ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2206038

Tirzepatide Once Weekly for the Treatment of Obesity At week 72, more participants in the tirzepatide groups had reductions in body weight of 10% or more, 15% or more, and 20% or more from baseline ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S126236362500031X

Real-world use and effectiveness of tirzepatide among ... In the current study, individuals who persisted on tirzepatide for 6 months experienced mean weight reduction of 12.9 % at 6 months post-index, although most ...

6. nature.com nature.com/articles/s41591-025-03978-z

A systematic review and meta-analysis of the efficacy and ... Tirzepatide was associated with a greater reduction of total body fat mass and a significantly lower reduction in total fat-free mass; similar ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12469573/

Real-World Safety Concerns of Tirzepatide Despite its efficacy, real-world safety data remain limited. This study analyzed post-marketing adverse events (AEs) associated with tirzepatide ...

8. frontiersin.org frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1593134/full

Efficacy and safety of tirzepatide for weight loss in patients ... This meta-analysis aims to evaluate efficacy and safety of tirzepatide for weight loss, including its dose-response relationship and adverse event profile.