Retatrutide for Chronic Kidney Disease and Obesity

No longer recruiting at 47 trial locations

Overseen By Brandon Lawrence

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Eli Lilly and Company

Must be taking: Oral antihyperglycemics, Basal insulin

Must not be taking: DPP4 inhibitors, GLP-RA, Rapid insulins

Disqualifiers: Obesity surgery, Type 1 diabetes, Hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called retatrutide (a GLP-1/GIP/glucagon tri-agonist) to assess its effects on kidney function in individuals who are overweight or have obesity and chronic kidney disease. Researchers aim to determine if retatrutide can improve kidney health, regardless of Type 2 Diabetes status. Participants will receive either retatrutide or a placebo (a substance with no therapeutic effect) for comparison. Those with chronic kidney disease and a body mass index (BMI) of 27 or higher might be suitable candidates. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does require that if you have Type 2 Diabetes, you should be on stable doses of up to 3 oral antihyperglycemic medications, with or without basal insulin, for at least 90 days before screening. Certain diabetes medications like DPP4 inhibitors and rapid-acting insulins should not have been used in the 90 days before screening.

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

Research has shown that retatrutide is as safe as other hormone-based treatments. In earlier studies focused on weight loss, participants generally tolerated retatrutide well. The side effects were manageable and similar to those of other treatments in the same category.

The studies reported that while some participants experienced side effects, they were not severe. Most side effects related to digestion, which is common with hormone treatments.

These results suggest that retatrutide is safe enough for further research in people with obesity and chronic kidney disease, regardless of Type 2 Diabetes status. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Retatrutide is unique because it targets both obesity and chronic kidney disease with a novel mechanism. Unlike traditional treatments that typically focus on either metabolic issues or kidney function separately, retatrutide works as a multifunctional peptide agonist, which can potentially improve both conditions simultaneously. Researchers are excited about this treatment because its dual-action approach could lead to more comprehensive health benefits, offering hope for better management of these interconnected health problems. Additionally, retatrutide is administered subcutaneously, which might provide a convenient and effective alternative to current oral or intravenous therapies.

What evidence suggests that retatrutide might be an effective treatment for chronic kidney disease and obesity?

Research has shown that retatrutide, which participants in this trial may receive, offers promising results for treating obesity. In one study, adults with obesity who took retatrutide for 48 weeks lost a significant amount of weight. Retatrutide targets three different areas in the body to help manage weight and related health issues. While more data continues to emerge, similar treatments have improved kidney health by addressing issues like high blood sugar. These early findings suggest that retatrutide could potentially help people with both chronic kidney disease and obesity. ^{1 3 5 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 overweight or obesity and chronic kidney disease, with or without Type 2 Diabetes. Participants must have a BMI ≥27 kg/m², stable treatment for at least 90 days, and specific HbA1c levels depending on their diabetes status. Exclusions include recent significant weight change, certain diabetes medications within the last 90 days, and a history of cancer in the past five years.

Inclusion Criteria

I have been diagnosed with chronic kidney disease.

My diabetes is under control with diet, exercise, or up to 3 medications.

Have a body mass index (BMI) ≥27 kilogram/square meter (kg/m²)

Exclusion Criteria

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

I have hepatitis.

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 multiple doses of retatrutide or placebo subcutaneously

24 weeks

Regular visits for dosing and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Retatrutide (LY3437943)

Trial Overview The study tests Retatrutide (LY3437943) to see its effects on kidney function in people who are overweight or obese with chronic kidney disease. Some participants will receive LY3437943 while others will get a placebo (a substance with no active drug). The trial lasts approximately 31 weeks.

How Is the Trial Designed?

Group I: Retatrutide Experimental Treatment 1 Intervention

Participants will receive multiple doses of retatrutide subcutaneously (SC)

Group II: Placebo Placebo Group 1 Intervention

Participants will receive LY3437943

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 phase 2 study involving 316 participants with poorly controlled type 2 diabetes, the dual receptor agonist LY3298176 demonstrated significantly better glucose control and weight loss compared to dulaglutide, with a dose-dependent reduction in HbA1c levels.

LY3298176 was generally well-tolerated, with gastrointestinal side effects being the most common but mostly mild to moderate, indicating a favorable safety profile for this new treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparator-controlled phase 2 trial. Frias, JP., Nauck, MA., Van, J., et al.[2022]

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 12-week study involving 72 adults with type 2 diabetes, the multi-receptor agonist LY3437943 demonstrated a good safety profile, with gastrointestinal disorders being the most common side effects.

LY3437943 significantly reduced daily plasma glucose and HbA1c levels, as well as body weight, in a dose-dependent manner, supporting its potential for once-weekly dosing and further development in treating type 2 diabetes and obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. Urva, S., Coskun, T., Loh, MT., et al.[2022]

LY3298176, a dual GIP and GLP-1 receptor agonist, demonstrated significant improvements in glycemic control and body weight reduction in both preclinical studies and a Phase 1b trial involving 142 subjects with type 2 diabetes mellitus (T2DM).

The most common side effects were mild to moderate gastrointestinal issues, which were dose-dependent, indicating that while LY3298176 is effective, monitoring for these side effects is important during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Coskun, T., Sloop, KW., Loghin, C., et al.[2021]

In a study involving 9901 participants with type 2 diabetes, long-term use of the GLP-1 receptor agonist dulaglutide significantly reduced the risk of adverse renal outcomes compared to placebo, with a hazard ratio of 0.85, indicating a 15% lower risk.

The most notable benefit was observed in the prevention of new macroalbuminuria, where dulaglutide reduced the incidence by 23% (hazard ratio 0.77), highlighting its potential to protect kidney function in diabetic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial. Gerstein, HC., Colhoun, HM., Dagenais, GR., et al.[2020]

Glucagon-like peptide-1 receptor agonists are recommended for patients with diabetic kidney disease, suggesting they may have beneficial effects on kidney health in this population.

The recommendation indicates a growing recognition of the role these medications can play in managing complications associated with diabetes, particularly in protecting kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of glucagon-like peptide-1 receptor agonists on kidney function and safety in type 2 diabetes patients. Kim, MK., Kim, DM.[2021]

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. jci.org jci.org/articles/view/194749

GLP-1 agonists in the treatment of chronic kidney disease ... Specifically, GLP-1 receptor agonists favorably influence relevant risk factors for kidney disease, including hyperglycemia, elevated blood ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12304053/

Triple Agonism Based Therapies for Obesity - PMC Retatrutide is the first triple agonist (acting on GLP-1/GIP/glucagon receptors) with published phase 2 data in people with obesity as well as ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2212877825000365

A once-daily GLP-1/GIP/glucagon receptor tri-agonist ... NN1706 lowers body weight & improves glycemic control in obese rodents and monkeys. NN1706 treatment led to 8.2% weight loss from baseline after 10 weeks.

5. 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 The results indicate that retatrutide has an overall safety and tolerability profile similar to other nutrient-stimulated hormone-based ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11536522/

The “Weight” for a New Agent Is Almost Over Ongoing phase II and III studies aim to further evaluate the safety and efficacy of retatrutide as a novel triagonist for obesity treatment.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05936151

NCT05936151 | A Study of Retatrutide (LY3437943) on ... The main purpose of this study is to investigate the effect of retatrutide on renal function in participants with overweight or obesity and chronic kidney ...