Retatrutide for Chronic Kidney Disease and Obesity

Recruiting at 45 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 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

146 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Retatrutide for chronic kidney disease and obesity?

Research shows that Retatrutide, which targets specific receptors involved in metabolism, has been effective in lowering blood sugar and body weight in people with type 2 diabetes. Additionally, similar drugs that target GLP-1 receptors have shown benefits for kidney function in diabetes patients. ^{1 2 3 4 5}

Is Retatrutide safe for humans?

Retatrutide has been studied for safety in people with type 2 diabetes and obesity. In these studies, it was generally well-tolerated, but like any medication, it may have side effects. Always discuss potential risks with your doctor. ^{1 2 3 6 7}

How is the drug Retatrutide unique for treating chronic kidney disease and obesity?

Retatrutide is unique because it targets three different hormone receptors (GLP-1, GIP, and glucagon) in one drug, which may help manage both obesity and related conditions like type 2 diabetes more effectively than treatments targeting only one or two of these receptors. ^{1 2 3 6 8}

What is the purpose of this trial?

This trial is testing a medication called retatrutide to see if it can help improve kidney function. The study focuses on people who are overweight or obese and have chronic kidney disease, with or without Type 2 Diabetes. The goal is to find out if this medication can make their kidneys work better.

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 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

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

Treatment Details

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.

Participant Groups

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

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 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]

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]

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]

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]

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]

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]

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. England pubmed.ncbi.nlm.nih.gov

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

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

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

4. Japan pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial. [2020]

6. England 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. [2022]

7. England 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. [2022]

8. Germany 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. [2021]