Retatrutide for Type 2 Diabetes and Obesity

(TRIUMPH-2 Trial)

Not currently recruiting at 149 trial locations

Overseen By Mira Baron

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Must not be taking: Weight loss drugs, Stimulants

Disqualifiers: Type 1 diabetes, Thyroid carcinoma, Pancreatitis, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 24

Duration: 80 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of a new treatment called retatrutide for individuals with type 2 diabetes who are also overweight or have obesity. Researchers aim to determine if retatrutide can help manage blood sugar levels and support weight loss. Some participants will also have obstructive sleep apnea (a condition where breathing stops and starts during sleep) to assess the treatment's impact on sleep. Individuals with type 2 diabetes, a BMI of 27 or higher, and unsuccessful dieting attempts may find this trial suitable. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to the development of a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be on stable treatment for Type 2 Diabetes for at least 90 days before joining. If you use certain medications like stimulants or hypnotics, you should have stopped them at least 3 months before the trial.

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

Research has shown that retatrutide is generally safe. A previous study found it to be as safe as other approved treatments for type 2 diabetes, with most participants tolerating it well. Another study reported that retatrutide led to significant weight loss and improved metabolism without major safety concerns.

Overall, retatrutide's safety profile is similar to other medications for diabetes and obesity. While all treatments can have side effects, current data suggest that retatrutide is safe for most people in these studies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for type 2 diabetes?

Retatrutide is unique because it targets multiple pathways associated with type 2 diabetes and obesity, potentially offering more comprehensive management of these conditions. Unlike current treatments, which often focus on a single mechanism like insulin regulation, retatrutide is a multi-receptor agonist, meaning it activates more than one type of receptor to achieve its effects. This approach could lead to better blood sugar control and more significant weight loss compared to existing options. Researchers are excited about its potential to not only improve metabolic outcomes but also enhance overall patient health.

What evidence suggests that retatrutide could be an effective treatment for type 2 diabetes and obesity?

Research has shown that retatrutide works well for people with type 2 diabetes and obesity. In this trial, participants will receive different doses of retatrutide or a placebo. Studies have found that those taking retatrutide lost significantly more weight than those taking a placebo. Specifically, one study showed participants lost an average of 16.9% of their body weight. Retatrutide also improved key health measures for managing diabetes. Early trials demonstrated it reduces body fat more effectively than some other treatments. Overall, these findings suggest retatrutide could be a promising option for managing type 2 diabetes and obesity. ^{1 2 3 6 7}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

This trial is for adults with Type 2 Diabetes and a BMI of at least 27, who have tried to lose weight unsuccessfully. Participants may also have moderate-to-severe obstructive sleep apnea (OSA) but should not be on certain OSA treatments or recent weight loss drugs. They mustn't have had significant weight changes recently or any history of specific thyroid cancers.

Inclusion Criteria

You have a moderate-to-severe obstructive sleep apnea, which is confirmed by a specific test called polysomnography.

I have used PAP therapy for 3 months and can stop it for 7 days before sleep studies.

You have tried to lose weight by changing your diet before, but it didn't work.

Exclusion Criteria

I have had pancreatitis.

I haven't used stimulants like modafinil or amphetamines in the last 3 months.

I have lost or gained more than 11 pounds in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive retatrutide or placebo subcutaneously

80 weeks

Up to 24 visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-9 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Retatrutide

Trial Overview The study tests the effectiveness and safety of Retatrutide in people with Type 2 Diabetes who are overweight or obese, including some with OSA. It's an approximately 89-week study involving up to 24 visits, comparing Retatrutide against a placebo.

How Is the Trial Designed?

Group I: Retatrutide Dose 3 Experimental Treatment 1 Intervention

Participants will receive retatrutide SC.

Group II: Retatrutide Dose 2 Experimental Treatment 1 Intervention

Participants will receive retatrutide SC.

Group III: Retatrutide Dose 1 Experimental Treatment 1 Intervention

Participants will receive retatrutide subcutaneously (SC).

Group IV: Placebo Placebo Group 1 Intervention

Participants will receive placebo.

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

In a phase 2 trial with 338 adults, retatrutide significantly reduced body weight over 48 weeks, with the highest dose (12 mg) leading to an average weight loss of 24.2% compared to only 2.1% in the placebo group.

While retatrutide was effective, the most common side effects were gastrointestinal issues, which were generally mild to moderate and could be managed by starting with a lower dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. Jastreboff, AM., Kaplan, LM., Frías, JP., et al.[2023]

In a phase 2 clinical trial, retatrutide demonstrated significant weight loss in participants, with reductions ranging from -7.2% to -18% over 24 weeks, depending on the dosage (1 mg to 12 mg).

While retatrutide shows promise for treating obesity and type 2 diabetes, it also caused an increase in heart rate by up to 6.7 beats per minute, which could be a concern and may counteract some benefits of weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retatrutide showing promise in obesity (and type 2 diabetes). Doggrell, SA.[2023]

Retatrutide, a triple agonist targeting incretin receptors, has shown significant weight loss and reductions in glycated hemoglobin (HbA1c) in phase-2 trials for individuals with type 2 diabetes mellitus (T2DM), as well as substantial weight loss in non-T2DM individuals, although gastrointestinal side effects were noted.

Concerns about cardiovascular safety have emerged due to dose-dependent increases in heart rate and mild to moderate cardiac arrhythmias, highlighting the need for long-term cardiovascular outcome trials to assess its safety in obesity management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retatrutide: a triple incretin receptor agonist for obesity management. Ray, A.[2023]

In a phase 2 trial involving 281 participants with type 2 diabetes, retatrutide demonstrated significant improvements in glycaemic control, with reductions in HbA1c levels that were greater than placebo and comparable to standard treatments like dulaglutide.

Retatrutide also led to substantial weight loss, with reductions of up to 16.94% at higher doses, while maintaining a safety profile similar to other GLP-1 receptor agonists, with no severe hypoglycaemia or deaths reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA. Rosenstock, J., Frias, J., Jastreboff, AM., et al.[2023]

In a study involving approximately 32,800 users of exenatide, there was a modestly higher incidence of claims for thyroid malignancies compared to users of metformin or glyburide, but this association was not significant when focusing on inpatient claims.

Exenatide use was not linked to an increased risk of benign thyroid neoplasms or pancreatic cancer, suggesting it may be a safe option regarding these specific cancer risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of health insurance claims for thyroid neoplasm and pancreatic malignancy in association with exenatide: signal refinement using active safety surveillance. Dore, DD., Seeger, JD., Chan, KA.[2021]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2301972

Triple–Hormone-Receptor Agonist Retatrutide for Obesity In a phase 1b trial involving participants with type 2 diabetes, treatment with retatrutide resulted in a placebo-adjusted least-squares mean weight reduction ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12026077/

Efficacy and safety of retatrutide, a novel GLP-1, GIP, and ... Retatrutide demonstrated significant improvements in body weight and metabolic outcomes among adults with obesity and had an appropriate safety profile.

3. diabetes.org diabetes.org/newsroom/american-diabetes-association-highlights-novel-agent-retatrutide-results-substantial-weight-reduction-people-with-obesity-type-2-diabetes-during-late-breaking-symposium

San Diego, California People taking retatrutide also lost more weight than those who took placebo – the average weight reduction for the 12 mg group was 16.9% (17.2 ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0014299924007854

Retatrutide's role in modern obesity and diabetes therapy Clinical trials in phases 1 to 3 have demonstrated significant efficacy, highlighted by significant reductions in body weight and favorable ...

5. thelancet.com thelancet.com/journals/landia/article/PIIS2213-8587(25)00092-0/abstract

Retatrutide effects on body composition in type 2 diabetes In adults with type 2 diabetes, retatrutide significantly improved total body fat mass reduction compared with placebo and dulaglutide. The ...

6. fda.gov fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss

FDA's Concerns with Unapproved GLP-1 Drugs Used for ... FDA has warned companies that have illegally sold unapproved drugs containing semaglutide, tirzepatide or retatrutide that are falsely labeled “for research ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05929079

NCT05929079 | A Study of Retatrutide (LY3437943) in ... The purpose of this study is to is to evaluate the efficacy and safety of retatrutide in participants with type 2 diabetes in participants who have obesity ...