Retatrutide for Type 2 Diabetes

Recruiting at 53 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

480 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to investigate the efficacy and safety of retatrutide compared with placebo in participants with Type 2 Diabetes and inadequate glycemic control. The study will last about 11 months and may include up to 11 visits.

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.

What data supports the effectiveness of the drug Retatrutide for treating type 2 diabetes?

Retatrutide has shown promise in lowering blood sugar and body weight in people with type 2 diabetes, as seen in a phase 1 study. It works by activating certain receptors in the body that help control blood sugar and weight. ^{1 2 3 4 5}

What makes the drug Retatrutide unique for treating type 2 diabetes?

Retatrutide is unique because it targets three different receptors (GIP, GLP-1, and glucagon receptors) in one single treatment, which helps lower blood sugar and body weight, unlike other treatments that typically target only one receptor. ^{1 2 3 6 7}

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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 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]

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 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]

References

1. England 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. [2023]

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

Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. [2023]

3. England pubmed.ncbi.nlm.nih.gov

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

4. England 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. [2023]

5. Netherlands 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. [2022]

6. England pubmed.ncbi.nlm.nih.gov

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

7. Germany 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. [2022]