Orforglipron for Obesity

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called orforglipron, designed for individuals who are overweight or obese. The study examines how the body absorbs and processes the drug when taken as capsules or tablets. It also evaluates the drug's safety and potential side effects. Individuals who are generally healthy, have maintained a stable weight recently, and have a BMI between 27 and 40 may be suitable for this trial. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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

Research has shown that orforglipron, a new pill, was generally well-tolerated in past studies. It functions like some injectable treatments that help manage blood sugar levels, but it is taken as a pill. This could offer a convenient and safe option for individuals.

Earlier research found no major restrictions on food or water when taking orforglipron, suggesting it might easily integrate into daily life. Although the treatment remains under study, its safety record so far supports further testing. Since this trial is in the early stages, the main goal is to understand how orforglipron works in the body and to identify any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for obesity, like lifestyle changes, medications, and sometimes surgery, aim to reduce appetite or increase metabolism. But Orforglipron works differently by targeting GLP-1 receptors, which play a role in regulating appetite and glucose levels. This new mechanism of action could offer more effective weight management by helping to control hunger and improve metabolic health. Researchers are excited because Orforglipron is taken orally as a tablet or capsule, making it convenient compared to some injectable GLP-1 treatments currently available. This combination of a novel mechanism and easy administration could make a significant difference for people struggling with obesity.

What evidence suggests that orforglipron might be an effective treatment for obesity?

Research has shown that orforglipron, an oral pill, can aid weight loss in people with obesity. In one study, adults who took orforglipron for 72 weeks lost significantly more weight than those on a placebo, with an average weight loss of 12.4%. This treatment activates the GLP-1 receptor, similar to some injectable weight-loss medications. Orforglipron is taken once daily, which may be more convenient than injections. These findings suggest orforglipron effectively assists weight loss in overweight or obese individuals. Participants in this trial will receive different sequences of orforglipron doses, administered as either tablets or capsules at varying dose levels, to further evaluate its effectiveness and bioavailability. ^{1 2 4 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 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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

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

Up to 25 weeks

Treatment Part B

Participants receive different sequences of orforglipron doses administered as either tablet or capsule at test dose levels 1 to 6

Up to 22 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07153471

NCT07153471 | A Study of Orforglipron (LY3502970) in ... Each study will see how well and safely orforglipron works in people with obesity or overweight who have osteoarthritis (OA) of the knee with pain.

2. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/dom.15150

Orforglipron (LY3502970), a novel, oral non‐peptide glucagon ... Orforglipron may provide a safe and effective once-daily oral treatment alternative to injectable GLP-1RAs or peptide oral formulations without water and food ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40960239/

Orforglipron, an Oral Small-Molecule GLP-1 Receptor ... Conclusions: In adults with obesity, 72-week treatment with orforglipron led to significantly greater reductions in body weight than placebo ...

4. clinicaltrialsarena.com clinicaltrialsarena.com/news/eli-lillys-oral-glp-1ra-hits-endpoints-but-trails-novos-wegovy-in-weight-loss/

Eli Lilly's oral GLP-1RA hits endpoints, but trails Novo's ... Orforglipron led to 12.4% weight loss after 72 weeks while Novo Nordisk's oral therapy showed a 13.6% drop in weight.

5. pnas.org pnas.org/doi/10.1073/pnas.2014879117

Structural basis for GLP-1 receptor activation by ... LY3502970 is a partial agonist, biased toward G protein activation over β-arrestin recruitment at the GLP-1R. The molecule is highly potent and selective.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37344954/

Orforglipron (LY3502970), a novel, oral non-peptide ... ... Orforglipron had a pharmacodynamic and safety profile similar to that of injectable GLP-1RAs, which supports continued clinical development.

7. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/551535

A Study of Orforglipron (LY3502970) in Adolescent ... Efficacy, Safety, and Pharmacokinetics of Orforglipron Once Daily Oral Versus Placebo in Adolescent Participants Who Have Obesity, or Overweight With Weight ...