Orforglipron for Obesity

Recruiting at 7 trial locations

Overseen By Martin Kankam

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Eli Lilly and Company

Disqualifiers: Diabetes, Cardiovascular, Psychiatric, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

508 Participants Needed

Trial Summary

What is the purpose of this trial?

The main purpose of this study is to see how much of orforglipron (study drug) gets into the bloodstream and how long it takes the body to get rid of it when given as capsules compared to tablets in healthy overweight and obese participants. The safety and tolerability (side effects) of orforglipron when given as capsules and tablets will also be evaluated. The study will be conducted in two parts, with part A and B lasting up to approximately 25 and 22 weeks each respectively, including the screening period.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the study is for healthy participants, it's possible that taking certain medications might affect eligibility. Please consult with the study team for specific guidance.

What data supports the effectiveness of the drug Orforglipron for obesity?

Research shows that Orforglipron, a drug that helps control blood sugar, also increased weight loss in people with obesity over 26 weeks. ^{1 2 3 4 5}

Is orforglipron safe for humans?

Orforglipron has been studied for safety in people with type 2 diabetes and obesity. In these studies, it was generally well-tolerated, meaning most people did not experience serious side effects. ^{1 2 3 4 5}

What makes the drug Orforglipron unique for treating obesity?

Orforglipron is unique because it is an oral, non-peptide drug that targets the glucagon-like peptide-1 (GLP-1) receptor, which is different from many other obesity treatments that are injectable. This makes it more convenient for patients who prefer a pill over an injection. ^{1 2 3 4 5}

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 who are overweight or obese. Participants will be given the study drug, Orforglipron, in two different forms: capsules and tablets. The trial aims to understand how the body absorbs and processes these forms.

Inclusion Criteria

Participants who are overtly healthy as determined by medical history and physical examination

I am committed to following the study's requirements for its entire duration.

Have venous access sufficient to allow for blood sampling

Exclusion Criteria

I have trouble swallowing pills.

Have hemoglobin A1c (HbA1c) level of 6.5 percent (%) or greater

I have had major depression or psychiatric issues in the past 2 years.

Treatment Details

Interventions

• Orforglipron

Trial Overview The focus of this study is on comparing the absorption into the bloodstream and elimination from the body of Orforglipron when administered as a tablet versus a capsule. It's divided into two parts, each lasting about 22-25 weeks including screening.

Participant Groups

Group I: Part B: BE (bioequivalence) study: Cohort 1 and 2: Orforglipron Experimental Treatment 1 Intervention

Participants will receive different sequences of orforglipron doses administered as either tablet (different dose levels) or capsule (test dose levels 1 to 6).

Group II: Part A: Relative bioavailability study: Cohort 1 and 2: Orforglipron Experimental Treatment 1 Intervention

Participants will receive different sequences of orforglipron doses administered as either tablet or capsule at different dose levels.

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 26-week phase 2 trial involving 383 participants with type 2 diabetes, orforglipron significantly reduced HbA1c levels by up to -2.10% compared to placebo and showed greater weight loss of up to -10.1 kg, indicating its efficacy as a treatment option.

The safety profile of orforglipron was comparable to other GLP-1 receptor agonists, with most adverse events being mild to moderate gastrointestinal issues, suggesting it may be a safer and more convenient alternative to injectable treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral orforglipron in patients with type 2 diabetes: a multicentre, randomised, dose-response, phase 2 study. Frias, JP., Hsia, S., Eyde, S., et al.[2023]

In a Phase 1b trial involving 68 participants with type 2 diabetes, orforglipron (LY3502970) demonstrated significant reductions in HbA1c levels (by -1.5% to -1.8%) and body weight (by -0.24 to -5.8 kg) compared to placebo, which only showed a -0.4% change in HbA1c.

Orforglipron was generally well tolerated, with gastrointestinal side effects similar to those seen with other GLP-1 receptor agonists, suggesting it may be a safe and effective oral alternative to injectable treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Orforglipron (LY3502970), a novel, oral non-peptide glucagon-like peptide-1 receptor agonist: A Phase 1b, multicentre, blinded, placebo-controlled, randomized, multiple-ascending-dose study in people with type 2 diabetes. Pratt, E., Ma, X., Liu, R., et al.[2023]

A study involving adults with obesity demonstrated that the daily oral GLP-1 receptor agonist orforglipron effectively aids in weight loss, showcasing its potential as a treatment option for obesity.

The findings suggest that orforglipron may offer a convenient oral alternative to traditional injectable GLP-1 receptor agonists, enhancing patient adherence to obesity management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In obesity or overweight without diabetes, orforglipron increased weight loss at 26 wk. Lau, D.[2023]

In a phase 2 trial involving 272 adults with obesity, the oral GLP-1 receptor agonist orforglipron resulted in significant weight loss, with participants losing between 8.6% to 14.7% of their body weight by week 36, compared to only 2.3% in the placebo group.

Orforglipron was generally well-tolerated, with mild to moderate gastrointestinal side effects being the most common adverse events, leading to discontinuation in 10-17% of participants, similar to the safety profile of injectable GLP-1 receptor agonists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity. Wharton, S., Blevins, T., Connery, L., 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral orforglipron in patients with type 2 diabetes: a multicentre, randomised, dose-response, phase 2 study. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Orforglipron (LY3502970), a novel, oral non-peptide glucagon-like peptide-1 receptor agonist: A Phase 1b, multicentre, blinded, placebo-controlled, randomized, multiple-ascending-dose study in people with type 2 diabetes. [2023]

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

In obesity or overweight without diabetes, orforglipron increased weight loss at 26 wk. [2023]

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

Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity. [2023]

5. 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]