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

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The goal of this pilot clinical trial is to determine the effectiveness of Tirzepatide in patients with persistent obesity (BMI \> 30) 12 months after bariatric surgery (Roux-en-Y Gastric Bypass). The investigators also aim to determine the frequency of side effects with Tirzepatide in this patient population. Patients who take tirzepatide 12 months after bariatric surgery will be compared to patients who continue with the current standard of care for patients who have previously undergone Gastric Bypass Surgery.

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 tirzepatide safe for humans?

Tirzepatide has been shown to be generally safe in humans, with common side effects including nausea, vomiting, diarrhea, and constipation, especially at higher doses. It has also been associated with a reduction in certain cardiovascular events, indicating a favorable safety profile in this regard. ^{1 2 3 4 5}

How does the drug tirzepatide differ from other treatments for obesity after bariatric surgery?

Tirzepatide is unique because it is a dual agonist, targeting both GIP and GLP-1 receptors, which helps in reducing body weight and improving insulin sensitivity more effectively than other treatments. This dual action is not commonly found in other obesity treatments, making it a novel option for weight management after bariatric surgery. ^{4 6 7 8 9}

What data supports the effectiveness of the drug Tirzepatide for obesity after bariatric surgery?

Tirzepatide has been shown to significantly reduce body weight in patients with type 2 diabetes and obesity, with some losing more than 10% of their initial weight. This suggests it could be effective for weight loss in patients who have had bariatric surgery. ^{1 4 5 9 10}

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.

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Published Research Related to This Trial

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]

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 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, 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 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]

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]

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 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]

Citations

1. England 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. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tirzepatide for treatment of overweight or obesity. A systematic review and meta-analysis. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Weight loss efficiency and safety of tirzepatide: A Systematic review. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Tirzepatide: Clinical review of the "twincretin" injectable. [2023]

5. Germany 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. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Tirzepatide, the Newest Medication for Type 2 Diabetes: A Review of the Literature and Implications for Clinical Practice. [2023]

7. Switzerland 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? [2023]

8. United States pubmed.ncbi.nlm.nih.gov

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

9. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Tirzepatide: A New Generation Therapeutic for Diabetes Type 2. [2023]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Tirzepatide: First Approval. [2022]