Retatrutide for Type 2 Diabetes

Not currently recruiting at 102 trial locations

Overseen By Sumana Gangi

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Must be taking: Basal insulin

Must not be taking: Weight loss drugs

Disqualifiers: Type 1 diabetes, Heart failure, 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: 22

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called retatrutide to determine its effectiveness in helping people with Type 2 Diabetes manage blood sugar levels, particularly those with kidney problems. Researchers aim to compare the efficacy of retatrutide to a placebo (a substance with no active medication) over approximately 14 months. Participants will receive varying doses of retatrutide or a placebo to identify the most effective option. Ideal candidates for this trial have Type 2 Diabetes, struggle to control blood sugar with insulin, have kidney issues, and maintain stable weight. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to 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. However, you must have been on a stable diabetes treatment with basal insulin, with or without metformin and/or SGLT2 inhibitor, for at least 90 days before joining the study.

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

Research has shown that retatrutide is as safe as other approved diabetes treatments. In studies involving people with type 2 diabetes, participants tolerated retatrutide well. It improved blood sugar levels and led to weight loss without major safety concerns.

Another study found that retatrutide's safety profile is similar to other incretin-based therapies, which are commonly used for diabetes. This suggests that retatrutide is generally safe for people based on current research. However, as with any treatment, side effects may occur, so staying informed and consulting a healthcare provider is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Retatrutide is unique because it targets multiple pathways that affect blood sugar and body weight, which is different from many current treatments for Type 2 Diabetes that typically focus on a single mechanism. This drug combines the actions of GLP-1, GIP, and glucagon receptor agonists, potentially offering more comprehensive control over diabetes symptoms. Researchers are excited about retatrutide because it could lead to better blood sugar management and weight loss compared to standard options like metformin or sulfonylureas, possibly enhancing overall patient outcomes.

What evidence suggests that retatrutide might be an effective treatment for Type 2 Diabetes?

Research has shown that retatrutide yields promising results for people with type 2 diabetes. In previous studies, participants taking retatrutide experienced significant improvements in body weight and overall health compared to those on a placebo. Specifically, individuals with type 2 diabetes lost a noticeable amount of body fat. This treatment works by affecting three hormone receptors, which helps control weight and improve blood sugar levels. Overall, early findings suggest retatrutide could effectively manage type 2 diabetes, particularly for those struggling with weight management. Participants in this trial will receive different doses of retatrutide or a placebo to further evaluate its effectiveness. ^{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 8 AM - 8 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 have moderate or severe kidney problems and whose blood sugar isn't well-controlled by long-acting insulin, possibly combined with metformin or SGLT2 inhibitors. Participants will be involved in the study for about 14 months and may need to attend up to 22 visits.

Inclusion Criteria

I've been on a stable diabetes treatment with basal insulin and possibly metformin or SGLT2 inhibitors for the last 90 days.

Have HbA1c ≥7.0% (53 mmol/mol) to ≤10.5% (91 mmol/mol)

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

Exclusion Criteria

I have Type 1 Diabetes.

I have had ketoacidosis or a severe diabetic episode in the last 6 months.

I have been cancer-free or in remission for less than 5 years.

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 for the duration of the study

52 weeks

Up to 22 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 Retatrutide against a placebo to see if it's better at controlling blood sugar levels in people with Type 2 Diabetes who also have kidney issues. The participants' responses to these treatments are compared over time.

How Is the Trial Designed?

Group I: Retatrutide Dose 3 Experimental Treatment 1 Intervention

Participants will receive retatrutide administered SC.

Group II: Retatrutide Dose 2 Experimental Treatment 1 Intervention

Participants will receive retatrutide administered SC.

Group III: Retatrutide Dose 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 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]

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]

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 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 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 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]

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/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. sciencedirect.com sciencedirect.com/science/article/abs/pii/S014067362301053X

Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, ... In people with type 2 diabetes, retatrutide showed clinically meaningful improvements in glycaemic control and robust reductions in bodyweight, with a safety ...

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 ...