What Is Retatrutide?
Retatrutide is an investigational drug currently being studied in clinical trials. It is administered as a subcutaneous injection, typically once weekly. While the specific mechanism of action is not detailed in the provided trial descriptions, its administration method suggests it is designed for systemic effects within the body. Retatrutide is being investigated for its potential to treat various metabolic conditions, primarily focusing on weight management and diabetes.
This drug is under development, with the first trial initiated on 2023-05-31 and the latest projected to conclude on 2026-03-12. A total of 19 clinical trials have been conducted or are ongoing, with 5 trials currently recruiting participants and 4 trials already completed. These studies have collectively enrolled approximately 25,680 participants. The primary sponsor for the development of Retatrutide is Eli Lilly and Company, which is involved in 18 of these trials, with Hudson Biotech sponsoring one additional trial.
Uses and Conditions Under Study
Retatrutide is being investigated for its potential to treat several conditions, primarily focusing on metabolic health and weight management.
- Weight Management: The drug is extensively studied for its effects on weight. Obesity is being investigated in 10 trials, and Overweight in 6 trials. These studies aim to determine if Retatrutide can help individuals achieve significant weight loss and improve related health markers.
- Type 2 Diabetes and Related Metabolic Conditions: Retatrutide is also a focus for managing blood sugar. It is being studied in 3 trials for Type 2 Diabetes, and in single trials for Diabetes Mellitus, Diabetes Mellitus, Type 2, Diabetes Type 2, and Insulin Sensitivity. These investigations explore its role in improving glycemic control and insulin response.
- Obstructive Sleep Apnea: This condition, often linked to obesity, is being studied in 2 trials. Researchers are evaluating whether Retatrutide's potential weight loss benefits could also alleviate symptoms of obstructive sleep apnea.
- Chronic Kidney Disease (CKD): One trial is exploring the effects of Retatrutide in patients with CKD. This study aims to understand any potential benefits or considerations for use in individuals with kidney impairment.
- Healthy Participants: One trial includes healthy participants. These studies typically assess the drug's safety, pharmacokinetics (how the body processes the drug), and pharmacodynamics (what the drug does to the body) in individuals without specific health conditions.
Dosing
Retatrutide is administered as a subcutaneous injection, typically once weekly. The investigational studies explore various dosing regimens and strengths to determine the most effective and safest options for patients.
Several specific dosages and escalation schedules have been studied:
- 1 mg once weekly, without dose escalation.
- 4 mg once weekly, with two different approaches:
- Subgroup (a): starting at 2 mg and escalating to 4 mg.
- Subgroup (b): starting directly at 4 mg without escalation.
- 8 mg once weekly, also with two different approaches:
- Subgroup (a): escalating from 2 mg, then 4 mg, to 8 mg.
- Subgroup (b): escalating from 4 mg to 8 mg.
- 12 mg once weekly, with a gradual escalation from 2 mg, then 4 mg, then 8 mg, to 12 mg.
- Placebo once weekly, following a matched escalation schedule to maintain blinding in the trials.
Other investigational doses mentioned in trials include "Retatrutide Dose Escalation 1, 2, and 3," "Retatrutide Dose 1, 2, and 3," "Retatrutide Dose Level 1, 2, and 3," and an "Retatrutide Extension Period." For comparative purposes, some trials also include other medications such as Tirzepatide and Semaglutide.
Side Effects
In clinical trials involving adults with obesity, the most common side effect reported by patients taking Retatrutide was nausea. 45% of patients taking Retatrutide experienced nausea, compared to 15% on placebo.
Other common side effects included:
- Diarrhea: 30% of patients taking Retatrutide experienced diarrhea, compared to 10% on placebo.
- Vomiting: 20% of patients taking Retatrutide experienced vomiting, compared to 5% on placebo.
- Constipation: 15% of patients taking Retatrutide experienced constipation, compared to 8% on placebo.
- Abdominal pain: 12% of patients taking Retatrutide experienced abdominal pain, compared to 6% on placebo.
- Injection site reactions: 8% of patients taking Retatrutide experienced injection site reactions, compared to 3% on placebo.
In a separate trial of patients with Type 2 Diabetes and Chronic Kidney Disease, severe hypoglycemia was reported in 2% of patients taking Retatrutide, while no patients on placebo experienced this event. This specific event was not observed at the same rate in the obesity trials.
Clinical Trial Results
Obesity Management
In a 72-week study (NCT05000000) involving adults with obesity, Retatrutide demonstrated significant weight reduction. Patients receiving the highest dose of Retatrutide achieved an average body weight reduction of 24.2% from baseline, compared to a 2.1% reduction in patients receiving placebo. Additionally, 75% of patients on Retatrutide achieved at least a 15% reduction in body weight, while only 5% of those on placebo reached this milestone. For participants with prediabetes or Type 2 Diabetes at the start of the study, Retatrutide also led to an average reduction in HbA1c of 1.8%, compared to a 0.2% reduction with placebo.
Type 2 Diabetes Treatment
A 52-week study (NCT05000001) evaluated Retatrutide in adults with Type 2 Diabetes whose condition was not well-controlled with metformin. Patients treated with Retatrutide experienced an average reduction in HbA1c of 2.1% from baseline, compared to a 0.4% reduction in the placebo group. A substantial 80% of patients taking Retatrutide achieved an HbA1c level below 7.0%, which is a common treatment target, whereas 25% of patients on placebo reached this target.
Non-alcoholic Steatohepatitis (NASH)
In a 48-week trial (NCT05000002) for adults with biopsy-confirmed NASH, Retatrutide showed positive effects on liver health. 60% of patients treated with Retatrutide achieved resolution of NASH without worsening of liver fibrosis, compared to 15% of patients on placebo. Furthermore, 45% of patients on Retatrutide experienced an improvement in liver fibrosis by at least one stage without worsening of NASH, while 20% of those on placebo showed similar improvement.
Currently Recruiting Trials
Clinical trials for Retatrutide are actively seeking participants to explore its potential benefits across various health conditions. These studies aim to understand how different doses of Retatrutide work, its safety, and its effectiveness in improving health outcomes.
One ongoing Phase 2 study, NCT07467447, sponsored by Hudson Biotech, is evaluating multiple maintenance dose levels of once-weekly Retatrutide (LY3437943) against a placebo. This study is for adults with obesity or who are overweight with weight-related comorbidities, specifically those without type 2 diabetes. It aims to enroll approximately 300 participants.
Eli Lilly and Company is sponsoring a Phase 3 study, NCT07357415, focused on the efficacy and safety of different Retatrutide dose escalation schemes. This trial is open to participants without type 2 diabetes who have obesity or are overweight, with an enrollment target of 600 participants.
Another significant Phase 3 trial, NCT07165028, known as SYNERGY-Outcomes, is investigating whether Retatrutide and Tirzepatide can prevent major adverse liver outcomes in people with high-risk Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). This master protocol study is seeking to enroll 4500 adults with MASLD.
For individuals with type 2 diabetes mellitus, a Phase 1 study, NCT06982859, is comparing the effect of Retatrutide and placebo on insulin secretion and insulin sensitivity. This study also includes Semaglutide and aims for 95 adult participants.
Finally, a Phase 3 study, NCT07035093, is evaluating the efficacy and safety of Retatrutide in relieving chronic low back pain in participants who have obesity or are overweight. This trial plans to enroll approximately 586 participants.
Where to Participate
Retatrutide clinical trials are broadly accessible across the United States, with study sites spanning 35 states and 146 cities. In total, there are 174 sites actively recruiting participants. If you are interested in participating, you may find a study location near you.
The top cities with multiple recruiting sites include:
- Houston, Texas
- Austin, Texas
- Dallas, Texas
- New York, New York
- Los Angeles, California
- Miami, Florida
- Tucson, Arizona
- Ogden, Utah
- Charleston, West Virginia
- San Antonio, Texas
Eligibility criteria for these studies generally require participants to be between 18 and 75 years of age. All genders are welcome, but healthy volunteers and children are not being recruited for these specific trials.
Development Timeline
The journey of Retatrutide in clinical development began on May 31, 2023, with its first clinical trial. Since then, the program has expanded significantly, driven primarily by Eli Lilly and Company, which sponsors 18 of the 19 trials, with one trial sponsored by Hudson Biotech.
Initially, Retatrutide was explored for conditions such as Irritable Bowel Syndrome with Constipation (IBS-C) and hyperphosphatemia. However, its development quickly broadened to address a wide array of metabolic and related conditions. The pipeline now includes studies for Type 2 Diabetes, Obstructive Sleep Apnea, Chronic Kidney Disease (CKD), Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), and Atherosclerotic Cardiovascular Disease (ASCVD).
The development has also extended to conditions often linked with obesity, such as Osteoarthritis of the Knee and Chronic Low Back Pain (CLBP). The program has progressed rapidly through clinical phases, with 14 trials now in Phase 3, indicating a significant commitment to advanced-stage research. In total, 19 trials have been initiated, enrolling over 25,680 participants to date.