LY3938577 for Type 2 Diabetes

Recruiting at 3 trial locations

Overseen By Nitendra Agarwal

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Eli Lilly and Company

Must not be taking: Sulfonylureas, Thiazolidinediones, Insulin, others

Disqualifiers: Proliferative retinopathy, Severe neuropathy, others

Compensation: Varies

Number of Visits: Unknown

66 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

If you are taking sulfonylurea, thiazolidinedione, alpha-glucosidase inhibitor, glucagon-like peptide-1 receptor agonist, or insulin, you must stop these medications at least 3 months before joining the trial.

What makes the drug LY3938577 unique for treating type 2 diabetes?

LY3938577 is unique because it likely acts as a multi-receptor agonist, similar to LY3437943, targeting glucagon, GIP, and GLP-1 receptors, which can help manage both blood sugar levels and weight in people with type 2 diabetes. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial tests a new drug, LY3938577, to see if it is safe for healthy people and those with Type 2 Diabetes. The study will check how well people tolerate the drug over several weeks.

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 healthy adults and those with Type 2 Diabetes Mellitus (T2DM). Healthy participants should have a BMI of 18.5-32 kg/m², while T2DM participants can have up to 40 kg/m². T2DM should be diagnosed over a year ago. People with severe eye or nerve complications, recent steroid therapy, or participation in another study recently cannot join.

Inclusion Criteria

I cannot become pregnant or get someone pregnant.

I am generally healthy as confirmed by a medical check-up.

My BMI is within the required range for my health status.

Exclusion Criteria

I have severe eye or nerve problems.

I have been on long-term steroid treatment in the last 3 months.

Are currently enrolled in another clinical study trial involving medical research, or have participated within the last 30 days in a clinical study involving an investigational product

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Treatment Part A

Participants receive a single dose of LY3938577 or placebo in healthy participants and participants with Type 2 Diabetes Mellitus

4 weeks

Treatment Part B

Participants with Type 2 Diabetes Mellitus receive multiple doses of LY3938577

10 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• LY3938577

Trial Overview The safety and tolerability of LY3938577 are being tested on two groups: healthy individuals and those with T2DM. Part A involves a single dose for both types of participants; Part B gives multiple doses to only the T2DM group. The study compares LY3938577 against Insulin degludec and placebo over approximately six to ten weeks.

Participant Groups

Group I: LY3938577 (Part B) Experimental Treatment 1 Intervention

LY3938577 administered SC.

Group II: LY3938577 (Part A) Experimental Treatment 1 Intervention

LY3938577 administered Subcutaneously (SC).

Group III: Insulin degludec (Part A) Active Control 1 Intervention

Insulin degludec administered SC.

Group IV: Insulin degludec (Part B) Active Control 1 Intervention

Insulin degludec administered SC.

Group V: Placebo (Part A) Placebo Group 1 Intervention

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 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]

LY2605541, a new basal insulin, was well-tolerated in patients with type 2 diabetes, showing a stable pharmacokinetic profile with minimal fluctuations and a duration of action lasting at least 24 hours.

The treatment led to significant reductions in fasting blood glucose levels and prandial insulin doses without causing severe hypoglycemia, indicating its efficacy and safety for managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Steady-state pharmacokinetics and glucodynamics of the novel, long-acting basal insulin LY2605541 dosed once-daily in patients with type 2 diabetes mellitus. Sinha, VP., Howey, DC., Choi, SL., 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

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]

2. 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]

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

Steady-state pharmacokinetics and glucodynamics of the novel, long-acting basal insulin LY2605541 dosed once-daily in patients with type 2 diabetes mellitus. [2022]

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

Evaluation of Efficacy and Safety of the Glucagon Receptor Antagonist LY2409021 in Patients With Type 2 Diabetes: 12- and 24-Week Phase 2 Studies. [2022]

5. 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]