Retatrutide for Type 2 Diabetes

Not currently recruiting at 54 trial locations

Overseen By There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Must not be taking: Insulin, Antihyperglycemics, Weight loss drugs

Disqualifiers: Type 1 diabetes, Severe hypoglycemia, 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: 11

Duration: 11 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called retatrutide for individuals with Type 2 Diabetes who struggle to control their blood sugar levels. Researchers aim to evaluate retatrutide's effectiveness compared to a placebo (a substance without active medicine) and ensure its safety. Participants will receive varying doses of retatrutide or a placebo over approximately 11 months. Those with Type 2 Diabetes who haven't used diabetes medications for at least 90 days and maintain a stable weight may be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

If you are currently taking diabetes medications, you must stop them at least 90 days before joining the trial. The trial is for people who haven't used diabetes medications recently.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown retatrutide to be safe. Research indicates that retatrutide is generally well-tolerated, with a safety profile similar to other approved treatments for type 2 diabetes. Reported side effects were usually mild and resembled those of similar treatments. These findings suggest that many patients can use retatrutide safely. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Type 2 Diabetes?

Unlike standard treatments for type 2 diabetes, which often include medications like metformin or insulin, retatrutide is unique because it targets multiple pathways involved in glucose and weight regulation. This investigational drug acts on the GLP-1, GIP, and glucagon receptors, potentially offering a more comprehensive approach to managing blood sugar levels and promoting weight loss. Researchers are excited about retatrutide because it has shown promise in not only controlling blood sugar but also in possibly reducing body weight, which is a significant concern for many patients with type 2 diabetes. Additionally, retatrutide is administered via a subcutaneous injection, which might provide convenience and improve adherence compared to oral medications that need to be taken multiple times a day.

What evidence suggests that this trial's treatments could be effective for Type 2 Diabetes?

Research has shown that retatrutide can greatly aid people with type 2 diabetes in managing their condition. In studies, retatrutide significantly decreased body fat and improved food processing in the body. Participants in this trial will receive varying doses of retatrutide or a placebo. Those taking retatrutide lost more weight than those on a placebo. Specifically, one group lost an average of 16.9% of their weight. These findings suggest that retatrutide might effectively improve blood sugar control for those with type 2 diabetes. ^{1 2 3 4 6}

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 who haven't been able to control their blood sugar levels through diet and exercise alone. Participants should be committed to the study duration of about 11 months and up to 11 visits.

Inclusion Criteria

Are of stable weight for at least 90 days prior to screening

I have Type 2 Diabetes.

Have HbA1c ≥ 7.0% to ≤ 9.5%

Exclusion Criteria

Have any lifetime history of a suicide attempt

I have Type 1 Diabetes.

I have had or am planning to have surgery for weight loss.

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 administered subcutaneously

11 months

Up to 11 visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Retatrutide

Trial Overview The trial is testing the effectiveness and safety of a new medication called Retatrutide compared to a placebo, which has no active ingredients, in managing blood sugar levels in people with Type 2 Diabetes.

How Is the Trial Designed?

Group I: Retatrutide Dose Level 3 Experimental Treatment 1 Intervention

Participants will receive retatrutide administered SC.

Group II: Retatrutide Dose Level 2 Experimental Treatment 1 Intervention

Participants will receive retatrutide administered SC.

Group III: Retatrutide Dose Level 1 Experimental Treatment 1 Intervention

Participants will receive retatrutide administered subcutaneously (SC).

Group IV: Placebo Placebo Group 1 Intervention

Participants will receive placebo administered SC.

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 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]

In a 24-week study involving 2202 patients with type 2 diabetes, both intensification strategies—either increasing the dose of long-acting insulin glargine or adding a rapid-acting insulin analogue—resulted in similar reductions in HbA1c levels (0.8% for glargine titration and 0.9% for glargine plus RAIA), indicating both methods are effective.

The study found that both strategies had low rates of hypoglycemic episodes, with no significant difference in safety, suggesting that either approach can be safely used to manage patients not achieving glycemic targets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Titration of basal insulin or immediate addition of rapid acting insulin in patients not at target using basal insulin supported oral antidiabetic treatment - A prospective observational study in 2202 patients. Siegmund, T., Pfohl, M., Forst, T., et al.[2022]

In a Phase II study involving 251 treatment-naive Chinese patients with type 2 diabetes, the PEGylated exenatide injection PB-119 demonstrated significant reductions in HbA1c levels compared to placebo, with mean differences of up to -12.89 mmol/mol after 12 weeks.

PB-119 was found to be safe and well-tolerated, with no serious adverse events or severe hypoglycemia reported during the study, indicating its potential as a reliable treatment option for managing glycemic control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of PEGylated exenatide injection (PB-119) in treatment-naive type 2 diabetes mellitus patients: a Phase II randomised, double-blind, parallel, placebo-controlled study. Ji, L., Du, Y., Xu, M., et al.[2022]

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 the TROPHIES study, which followed 24 months of treatment in adults with type 2 diabetes starting their first injectable medication, both dulaglutide and liraglutide showed improvements in health-related patient-reported outcomes (PROs).

Patients using dulaglutide reported greater satisfaction and a more positive self-perception regarding weight compared to those using liraglutide, suggesting that dulaglutide may offer a more favorable experience for patients starting GLP-1 receptor agonist therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Real-World Observational Prospective Study of Health Outcomes with Dulaglutide and Liraglutide in Type 2 Diabetes Patients (TROPHIES): Final patient-reported outcomes at 24 months. Boye, KS., Lebrec, J., Dib, A., et al.[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]

Exenatide effectively lowers fasting plasma glucose and HbA1c levels in type 2 diabetes patients who are not adequately controlled on other medications, working through mechanisms like enhancing insulin secretion and reducing glucagon levels.

The most common side effects of exenatide are nausea and vomiting, but the risk of acute pancreatitis appears to be similar to that of the general population with type 2 diabetes, suggesting it is relatively safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exenatide: clinical aspects of the first incretin-mimetic for the treatment of type 2 diabetes mellitus. Wajcberg, E., Tavaria, A.[2019]

Citations

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

Triple–Hormone-Receptor Agonist Retatrutide for Obesity In adults with obesity, retatrutide treatment for 48 weeks resulted in substantial reductions in body weight.

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/S2213858725000920

Effects of retatrutide on body composition in people with ... In adults with type 2 diabetes, retatrutide significantly improved total body fat mass reduction compared with placebo and dulaglutide.

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

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

6. 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 ...