Tirzepatide for Obesity

(TIRO-AF Trial)

Overseen By Jeannine M Ramsey, RN, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 2

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 This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 12 months

100 Participants Needed

Trial Summary

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. ^{1 2 3 4 5}

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. ^{2 3 4 6 7}

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. ^{1 2 3 4 8}

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.

Research Team

Leslie Cho, MD

Principal Investigator

The Cleveland Clinic

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.

My BMI is between 30 and 60.

Sinus rhythm at enrollment

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.

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)

Treatment Details

Interventions

• Tirzepatide

Trial Overview 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.

Participant Groups

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).

Who Is Running the Clinical Trial?

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

Findings from Research

Tirzepatide, administered once weekly, has been shown to be effective in promoting weight loss in individuals with obesity, as demonstrated in a clinical study.

The treatment not only aids in weight reduction but also improves metabolic health markers, making it a promising option for obesity management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In adults with obesity without diabetes, adding tirzepatide to a lifestyle intervention increased weight loss at 72 wk. Davidson, MB.[2022]

In a 72-week phase 3 trial involving 938 adults with obesity and type 2 diabetes, tirzepatide (10 mg and 15 mg) led to significant weight loss, with reductions of -12.8% and -14.7% respectively, compared to only -3.2% with placebo.

The safety profile of tirzepatide was generally favorable, with most adverse events being mild to moderate gastrointestinal issues, and serious adverse events were rare, indicating it is a safe option for weight management in this population.

NCBI (Pubmed)

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. Garvey, WT., Frias, JP., Jastreboff, AM., et al.[2023]

In a 72-week phase 3 trial involving 2539 adults with obesity, tirzepatide (5 mg, 10 mg, or 15 mg) resulted in significant weight loss, with mean reductions of -15.0%, -19.5%, and -20.9% respectively, compared to only -3.1% with placebo.

A high percentage of participants (85% to 91%) on tirzepatide achieved at least a 5% weight reduction, and many experienced improvements in cardiometabolic measures, although gastrointestinal side effects were the most common adverse events, mostly mild to moderate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide Once Weekly for the Treatment of Obesity. Jastreboff, AM., Aronne, LJ., Ahmad, NN., et al.[2023]

Tirzepatide, administered once weekly, was found to be effective in reducing obesity in individuals with type 2 diabetes, as demonstrated in a large phase 3 trial involving multiple centers.

The study was double-blind and placebo-controlled, ensuring robust results that support tirzepatide as a promising treatment option for weight management in this population.

NCBI (Pubmed)

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. Davidson, MB.[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, a new GLP-1 receptor agonist, was found to be more effective for weight loss compared to other GLP-1RAs like semaglutide and liraglutide, with significant weight loss observed in over 12,300 patients in the analysis.

While all GLP-1RAs were associated with gastrointestinal side effects, tirzepatide showed better efficacy outcomes for weight loss while maintaining a similar safety profile to other treatments.

NCBI (Pubmed)

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. Alkhezi, OS., Alahmed, AA., Alfayez, OM., et al.[2023]

Tirzepatide, a novel GLP-1 receptor agonist, has been shown to significantly reduce A1C levels and body weight in patients with type 2 diabetes compared to placebo and other active treatments.

The safety profile of tirzepatide is similar to other GLP-1 receptor agonists, with the most common side effects being mild to moderate gastrointestinal issues, and it does not increase the risk of hypoglycemia, making it a promising treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Tirzepatide in Adults With Type 2 Diabetes: A Perspective for Primary Care Providers. Kushner, P., Anderson, JE., Simon, J., et al.[2023]

In a phase 3b clinical trial involving 1428 adults with type 2 diabetes, tirzepatide significantly reduced HbA1c levels more than prandial insulin lispro after 52 weeks, achieving a mean HbA1c of 6.7% compared to 7.7% for insulin lispro.

Tirzepatide also led to greater weight loss (-9.0 kg) compared to insulin lispro (-3.2 kg) and had a much lower rate of hypoglycemia events, making it a safer option for patients inadequately controlled on basal insulin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide vs Insulin Lispro Added to Basal Insulin in Type 2 Diabetes: The SURPASS-6 Randomized Clinical Trial. Rosenstock, J., Frías, JP., Rodbard, HW., et al.[2023]

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]

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]

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

Tirzepatide Once Weekly for the Treatment of Obesity. [2023]

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]

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]

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]

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]

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]