Tirzepatide for Obesity After Bariatric Surgery

(GRABS-0 Trial)

Overseen By Jason M Samuels, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Vanderbilt University Medical Center

Must not be taking: Type 2 diabetes drugs, Glucocorticoids

Disqualifiers: Type I diabetes, Tobacco use, Pancreatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether Tirzepatide, a GIP/GLP-1 receptor agonist, can aid weight loss in individuals who remain obese (BMI over 30) one year after gastric bypass surgery. The study compares this treatment to the usual post-surgery care and examines the frequency of side effects with Tirzepatide. Individuals who underwent Roux-en-Y Gastric Bypass and still have a BMI over 30 after 12 months may qualify for this trial. As a Phase 2, Phase 3 trial, the research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking obesity treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are using medications for type 2 diabetes or systemic glucocorticoids, you may not be eligible to participate.

Is there any evidence suggesting that Tirzepatide is likely to be safe for humans?

Research has shown that tirzepatide, a drug under study for weight loss, has shown promise in earlier studies. Understanding its effects on users is important. In past research, most participants tolerated tirzepatide well. Some experienced side effects, mainly stomach-related, such as nausea or diarrhea, which were usually mild to moderate.

For those concerned about safety, tirzepatide is similar to other weight loss drugs. These drugs are known to aid weight loss, especially when combined with lifestyle changes. However, monitoring for any side effects and consulting a doctor if anything unusual occurs is always important.

Overall, while some side effects have been reported, most participants found the treatment manageable. Those considering joining a tirzepatide trial might find this information helpful in understanding its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Tirzepatide is unique for post-bariatric surgery obesity management because it combines two hormone actions into one treatment, targeting both GLP-1 and GIP receptors. Unlike standard care, which typically focuses on dietary guidance and lifestyle changes, tirzepatide directly influences metabolic pathways to regulate appetite and glucose levels. Researchers are excited because tirzepatide has shown promising results in reducing weight more effectively than traditional options, potentially offering a new way to enhance weight maintenance after gastric bypass surgery.

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

This trial will compare Tirzepatide with standard care for weight maintenance after gastric bypass surgery. Research has shown that Tirzepatide, a newer medication, yields promising results for weight loss. In particular, one study found that people taking Tirzepatide lost more weight over six months compared to those taking semaglutide, another well-known weight loss drug. This suggests it could be very effective for individuals struggling with obesity. Additionally, patients using medications like Tirzepatide often lose a significant amount of weight regained after weight-loss surgery. This treatment appears to be a helpful option for managing obesity post-surgery. ^{1 3 4 5 6}

Who Is on the Research Team?

Jason M Samuels, MD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for adults aged 30-65 with severe obesity (BMI > 50) who have had Roux-en-Y Gastric Bypass surgery. Participants must understand the study and consent to join. Exclusions include type I Diabetes, recent use of certain diabetes medications or tobacco products, history of pancreatitis or some cancers, uncontrolled hypertension, and significant heart issues.

Inclusion Criteria

My BMI was over 50 when I had bariatric surgery.

I am between 31 and 64 years old.

I understand the study and can give my consent.

Exclusion Criteria

Inability or unwillingness of a subject to give written informed consent or comply with the study protocol.

I have not taken any steroids in the last 28 days.

Pregnancy by urine testing, current lactation, or plans to become pregnant during the study period.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Tirzepatide with dose titration over 24 weeks or standard of care post-gastric bypass

24 weeks

Regular visits for dose titration and monitoring

Follow-up

Participants are monitored for safety, effectiveness, and weight regain after treatment

24 weeks

Periodic visits for monitoring

What Are the Treatments Tested in This Trial?

Interventions

• Tirzepatide

Trial Overview

The GRABS trial is testing Tirzepatide's effectiveness in patients post-bariatric surgery compared to those who only undergo the surgery. It aims to see if this drug can help further with weight loss and maintain health after the procedure.

How Is the Trial Designed?

Group I: Tirzepatide Group Experimental Treatment 1 Intervention

Participants in the TRZ cohort will initiate a standardized dose titration as described in the package insert. Participants will begin TRZ at 2.5 mg for four weeks and then increase by 2.5 mg every 4 weeks to a maximum dose of 15 mg. If subjects experience intolerable GI symptoms, they will be allowed to decrease to a lower dose by 2.5 mg for 2 weeks, at which point another attempt at an increased dose will be trialed. Should patients not tolerate a higher dose a second time, they will have the dose again lowered by 2.5 mg and kept at the lower dose for the remainder of the study, except for patients who do not tolerate two attempts at 5 mg. For patients who fail to titrate to at least 5 mg TRZ, a third attempt at an increased dose will be attempted 4 weeks after the second decrease in dose. These patients will then remain on 5 mg for the remainder of the intervention period. All participants receiving TRZ will be pooled in terms of outcomes measures.

Group II: Control - Standard of care Post-Gastric Bypass Surgery Experimental Treatment 1 Intervention

Patients randomized to the control arm will receive the standard of care for weight maintenance after gastric bypass including dietary guidance provided by the Vanderbilt Surgical Weight Loss handbook for 24 weeks. After 24 weeks, particiapnts in the control arm will crossover to the Tirzepatide arm and receive 24 weeks of TRZ following the same titration.

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Published Research Related to This Trial

Tirzepatide (Mounjaro™) is a new treatment for type 2 diabetes that acts on both GIP and GLP-1 receptors, showing strong results in lowering blood glucose and promoting weight loss based on evidence from five SURPASS clinical trials.

The safety profile of tirzepatide is similar to that of existing GLP-1 receptor agonists, making it a promising option for early intervention in managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug: Tirzepatide (Mounjaro™). Gettman, L.[2023]

In a systematic review of randomized controlled trials involving 5800 patients, tirzepatide was found to be highly effective for weight loss, with 78.22% achieving at least 5% weight loss and 32.28% achieving at least 15% weight loss.

Tirzepatide demonstrated superior weight loss compared to placebo and semaglutide, with a significant mean weight loss of -12.47 kg at the 5 mg dose, while showing a manageable safety profile with only a slight increase in gastrointestinal adverse events compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tirzepatide for treatment of overweight or obesity. A systematic review and meta-analysis. Tan, B., Pan, XH., Chew, HSJ., et al.[2023]

Tirzepatide, the first dual GIP/GLP-1 receptor co-agonist approved for type 2 diabetes, significantly reduces HbA1c levels (by 1.24 to 2.58%) and body weight (by 5.4-11.7 kg) in clinical trials involving type 2 diabetic patients, outperforming the selective GLP-1 RA semaglutide.

The safety profile of tirzepatide is similar to that of other GLP-1 receptor agonists, with common side effects including nausea and diarrhea, and it shows potential cardiovascular safety, as no significant increase in major adverse cardiovascular events was observed during the trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regrading glycaemic control and body weight reduction. Nauck, MA., D'Alessio, DA.[2022]

Tirzepatide is a novel medication that acts on both GIP and GLP-1 receptors, enhancing insulin secretion and reducing glucagon levels, which helps improve glycemic control in adults with type 2 diabetes mellitus (T2DM).

It received its first approval in the USA in May 2022 for T2DM treatment and is currently being studied for additional conditions like obesity, heart failure, and non-alcoholic steatohepatitis, indicating its potential for broader therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide: First Approval. Syed, YY.[2022]

Tirzepatide, approved in 2022, is a novel treatment for type 2 diabetes that acts on both GLP-1 and GIP pathways, showing significant efficacy in lowering blood sugar levels and promoting weight loss in various patient groups.

Clinical trials, including the SURPASS and SURMOUNT studies, indicate that tirzepatide has a safety profile similar to traditional GLP-1 receptor agonists, with common gastrointestinal side effects, making it a promising option for patients needing better glycemic and weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide: Clinical review of the "twincretin" injectable. Krauss, Z., Hintz, A., Fisk, R.[2023]

Tirzepatide significantly reduces body weight in patients with type 2 diabetes and obesity, with an average weight loss of -9.81 kg compared to placebo, based on a meta-analysis of 10 studies involving 9,873 patients.

While tirzepatide is effective for weight loss, it has a higher incidence of gastrointestinal side effects compared to placebo, although serious adverse events and hypoglycemia are less common, indicating a need for monitoring these reactions during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight loss efficiency and safety of tirzepatide: A Systematic review. Lin, F., Yu, B., Ling, B., et al.[2023]

Tirzepatide, a new medication approved by the FDA, acts as an agonist for both GLP-1 and GIP receptors, which helps improve blood sugar control in patients with type II diabetes when combined with diet and exercise.

This drug represents a significant advancement in diabetes management, offering a new approach to treatment by targeting multiple pathways involved in glucose regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide: A New Generation Therapeutic for Diabetes Type 2. Al-Horani, RA., Chedid, M.[2023]

Tirzepatide demonstrated a dose-dependent ability to lower HbA1c levels in adults with type 2 diabetes, with reductions ranging from -17.71 to -22.35 mmol/mol compared to placebo, and was also more effective in reducing body weight than other treatments.

While tirzepatide did not increase the risk of hypoglycaemia compared to placebo and showed lower rates than basal insulin, it was associated with a higher incidence of gastrointestinal side effects, particularly nausea and vomiting, especially at the 15 mg dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: a systematic review and meta-analysis. Karagiannis, T., Avgerinos, I., Liakos, A., et al.[2023]

Tirzepatide, a dual GIP and GLP-1 receptor agonist, showed significant reductions in Hemoglobin A1c levels (up to 3.02%) and weight loss in adults with uncontrolled type 2 diabetes, outperforming both placebo and active comparators like semaglutide.

The safety profile of tirzepatide was comparable to semaglutide regarding gastrointestinal adverse effects, and it did not increase the incidence of major cardiovascular events compared to insulin glargine, indicating it may be a valuable addition to diabetes treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide, the Newest Medication for Type 2 Diabetes: A Review of the Literature and Implications for Clinical Practice. Bradley, CL., McMillin, SM., Hwang, AY., et al.[2023]

Tirzepatide, a dual GIP and GLP-1 receptor agonist, has a safety profile similar to other GLP-1 receptor agonists, but higher doses (10mg and above) are associated with increased risks of hypoglycemia and treatment discontinuation.

In clinical trials involving 9818 patients, higher doses of tirzepatide led to more frequent gastrointestinal side effects like nausea, vomiting, and diarrhea, indicating that these adverse events are dose-dependent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of the safety of tirzepatide-a new dual GLP1 and GIP agonist - is its safety profile acceptable? Meng, Z., Yang, M., Wen, H., et al.[2023]

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The goal of this pilot clinical trial is to determine the effectiveness of Tirzepatide in patients with persistent obesity (BMI > 30) 12 months after ...