Tirzepatide for Obesity

(TIRO-AF Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Leslie Cho, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: The Cleveland Clinic

Must not be taking: GLP-1, DPP4i, GIP

Disqualifiers: Severe cardiopulmonary disease, Type 1 diabetes, Advanced cirrhosis, Active malignancy, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is a single center randomized double blind controlled study of patients (BMI\> 30 kg/m2) with obesity and Atrial Fibrillation (AFIB) randomized to Tirzepatide vs. placebo. It is expected that the significant weight loss with Tirzepatide will result in improved control, management, symptom severity, and burden of AFIB at 12 months.

Will I have to stop taking my current medications?

The trial requires that all anti-diabetic medications, including insulin, must be stable for at least 3 months before joining. If you are currently using GLP-1, DPP4i, or GIP/GLP-1 medications, you must have stopped them at least 6 months prior to participating.

What data supports the effectiveness of the drug Tirzepatide for obesity?

Research shows that Tirzepatide, when added to lifestyle changes, helps people with obesity lose more weight over 72 weeks. This drug has been effective in both people with and without type 2 diabetes, indicating its potential for weight management.

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Is tirzepatide safe for humans?

Tirzepatide has been studied for its safety in people with obesity and type 2 diabetes. It generally has a safety profile similar to other drugs in its class, with common side effects being mild to moderate stomach issues like nausea and diarrhea.

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How is the drug Tirzepatide unique for treating obesity?

Tirzepatide is unique because it combines two actions in one drug: it mimics hormones that help control blood sugar and appetite, making it effective for weight loss. Unlike other treatments, it is taken once a week, which can be more convenient for patients.

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Eligibility Criteria

This trial is for individuals with obesity (BMI over 30 kg/m2) and Atrial Fibrillation. Participants must meet specific health criteria to join, but the exact inclusion and exclusion details are not provided here.

Inclusion Criteria

My heart rhythm has been normal for at least 2 hours after treatment or during my last doctor's visit.

I am between 18 and 80 years old.

My BMI is between 30 and 60.

Exclusion Criteria

I have a serious heart valve problem and plan to have surgery within a year.

I had AFIB ablation in the last 6 months.

My kidney function is very low or I am on dialysis.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Treatment

Participants receive weekly subcutaneous injections of Tirzepatide or placebo, with dose escalation at weeks 4, 8, and 12

12 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Participant Groups

The study tests Tirzepatide against a placebo in managing Atrial Fibrillation symptoms in obese patients. It's a randomized, double-blind study meaning neither the participants nor the researchers know who gets the real treatment or placebo.

Group I: Tirzepatide Experimental Treatment 1 Intervention

Participants to inject weekly subcutaneous injections of Tirzepatide starting with dose 2.5mg, then increase dose by 2.5mg at week 4 (5mg), week 8 (7.5mg) and at week 12 (10mg) as tolerated.

Group II: Control Placebo Group 1 Intervention

Participants to inject weekly subcutaneous injections of normal saline starting with dose 2.5mg, then increase dose by 2.5mg at week 4 (5mg), week 8 (7.5mg) and at week 12 (10mg).

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Cleveland Clinic Cleveland, OH

Who Is Running the Clinical Trial?

The Cleveland Clinic Lead Sponsor

References

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

In adults with obesity without diabetes, adding tirzepatide to a lifestyle intervention increased weight loss at 72 wk. [2022] Label="SOURCE CITATION">Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387:205-16. 35658024.

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

Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. [2023] Weight reduction is essential for improving health outcomes in people with obesity and type 2 diabetes. We assessed the efficacy and safety of tirzepatide, a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, versus placebo, for weight management in people living with obesity and type 2 diabetes.

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

Tirzepatide Once Weekly for the Treatment of Obesity. [2023] Obesity is a chronic disease that results in substantial global morbidity and mortality. The efficacy and safety of tirzepatide, a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, in people with obesity are not known.

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

In adults with BMI ≥27 kg/m2 and type 2 diabetes, adding tirzepatide to a lifestyle intervention increased weight loss at 72 wk. [2023] Label="SOURCE CITATION" NlmCategory="UNASSIGNED">Garvey WT, Frias JP, Jastreboff AM, et al; SURMOUNT-2 investigators. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2023;402:613-626. 37385275.

5. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tirzepatide for treatment of overweight or obesity. A systematic review and meta-analysis. [2023] Recent studies suggest that tirzepatide, a dual glucose-dependent insulinotropic-peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA), has significant weight loss effects. This systematic review and meta-analysis aims to assess the efficacy and safety of tirzepatide for weight loss in patients with overweight or obesity.

6. England pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of glucagon-like peptide-1 receptor agonists for the management of obesity in adults without diabetes: A network meta-analysis of randomized clinical trials. [2023] Tirzepatide is a new glucagon-like peptide-1 receptor agonist (GLP-1RA) that has shown promising results for weight loss. A Bayesian network meta-analysis was conducted to compare the efficacy and safety of GLP-1RAs for obesity management. Embase and MEDLINE were searched looking for randomized clinical trials (RCTs) that evaluated the efficacy of GLP-1RAs for weight loss in patients without diabetes. The main efficacy outcomes evaluated were the mean change in actual and percentage weight loss and the proportion of patients with weight loss of ≥5%-20%. Main safety outcomes evaluated include nausea, vomiting, diarrhea, constipation, loss of appetite, pancreatitis, gallbladder-related disorders, and withdrawal due to adverse events. Seven RCTs with more than 12,300 patients were analyzed, including patients with body mass index (BMI) ≥ 30 kg/m2 , or BMI ≥ 27 kg/m2 with comorbidities. Weekly tirzepatide 10 and 15 mg resulted in more weight loss than weekly semaglutide 2.4 mg, daily semaglutide 0.4 mg, or liraglutide 3 mg. Tirzepatide and weekly semaglutide demonstrated comparable results but with significantly higher odds of achieving ≥5%-20% weight loss compared with liraglutide. GLP-1RAs triggered more gastrointestinal adverse events than placebo, with no in-between difference. Although all GLP-1RAs lead to significant weight reduction, tirzepatide was associated with better efficacy outcomes while having a comparable safety profile.

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

Efficacy and Safety of Tirzepatide in Adults With Type 2 Diabetes: A Perspective for Primary Care Providers. [2023] This article reviews the efficacy and safety data of tirzepatide, a once-weekly, novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 (GLP-1) receptor agonist approved in the United States, the European Union, and other regions for the treatment of type 2 diabetes. All doses of tirzepatide demonstrated superiority in reducing A1C and body weight from baseline versus placebo or active comparators. The safety profile of tirzepatide was consistent with that of the GLP-1 receptor agonist class, with mild to moderate and transient gastrointestinal side effects being the most common adverse events. With clinically and statistically significant reductions in A1C and body weight without increased risk of hypoglycemia in various populations, tirzepatide has demonstrated potential as a first-in-class treatment option for many people with type 2 diabetes.

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

Tirzepatide vs Insulin Lispro Added to Basal Insulin in Type 2 Diabetes: The SURPASS-6 Randomized Clinical Trial. [2023] Tirzepatide is a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist used for the treatment of type 2 diabetes. Efficacy and safety of adding tirzepatide vs prandial insulin to treatment in patients with inadequate glycemic control with basal insulin have not been described.