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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Tirzepatide to determine if it can help people with obesity and Atrial Fibrillation (AFIB) manage their condition more effectively. Researchers believe that significant weight loss with Tirzepatide might improve AFIB symptoms over a year. Participants will receive either Tirzepatide or a placebo (a harmless, inactive substance) to compare results. This trial may suit those with a BMI over 30, who experience AFIB symptoms, and can administer a weekly injection. As a Phase 2 trial, this research measures how well Tirzepatide works in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

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.

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

Research has shown that tirzepatide is generally well-tolerated for weight loss. In one study, adults with obesity experienced significant weight loss using tirzepatide, demonstrating its effectiveness. However, understanding its safety is also important.

Reports mention side effects like nausea and vomiting, which are common, but serious problems are rare. A review of multiple studies suggests that while tirzepatide is effective, more safety data from real-world use is still being gathered.

This trial is in an early stage and is still collecting detailed safety information. However, since tirzepatide is already used for other conditions, there is some confidence in its safety. Always consult a healthcare provider before joining a trial to ensure it is suitable. ^{1 2 3 4 5}

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

Tirzepatide is unique because it combines a dual-action mechanism that targets both the GLP-1 and GIP hormone receptors, which play a significant role in regulating appetite and blood sugar. Unlike the standard treatments for obesity, such as lifestyle changes, or medications like orlistat and phentermine that focus primarily on appetite suppression or fat absorption, Tirzepatide offers a novel approach by enhancing the body's natural ability to control hunger and manage energy use. Researchers are excited about Tirzepatide's potential to provide more effective weight loss with improved blood sugar control, setting it apart as a promising new strategy in obesity management.

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

Research has shown that Tirzepatide, which participants in this trial may receive, can aid in weight loss. One study found that individuals using Tirzepatide lost more than 10% of their body weight by week 72. Another study reported an average weight loss of 12.9% after just six months. Weight loss can help manage and reduce symptoms of obesity-related conditions, such as atrial fibrillation, an irregular heartbeat. This suggests that Tirzepatide might effectively help control these symptoms through weight loss. ^{1 4 6 7 8}

Who Is on the Research Team?

Leslie Cho, MD

Principal Investigator

The Cleveland Clinic

Are You a Good Fit for This Trial?

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.

Liver transaminase level >300 U/L

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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, 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]

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]

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 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]

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.