Orforglipron for Obesity

No longer recruiting at 30 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Disqualifiers: Diabetes, Obesity surgery, Hepatitis, Pancreatitis, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: Duration not specified

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test how well a new treatment called orforglipron (a GLP-1 receptor agonist) helps people maintain weight loss. Participants will take either orforglipron or a placebo (a pill with no active medicine) to determine orforglipron's effectiveness and safety. The trial seeks individuals who previously participated in the SURMOUNT-5 study and have no history of diabetes, pancreatitis, or certain liver issues. Those with these conditions may not be eligible. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking 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. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that orforglipron has a safety profile similar to other treatments called GLP-1 receptor agonists, commonly used for diabetes and obesity. Previous studies found that orforglipron is generally well-tolerated, with most participants not experiencing serious side effects. Unlike some similar treatments that require injections, it is taken as a pill.

While detailed safety data from this specific trial is not yet available, the treatment is in a late stage of testing. Earlier studies have not shown major safety concerns. For those considering joining a trial, these findings suggest that the treatment is considered safe enough for testing on a larger group of people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Orforglipron is unique because it offers a new approach to tackling obesity with its oral delivery method, making it easier to incorporate into daily routines compared to injectable treatments like GLP-1 receptor agonists. Most obesity treatments, such as liraglutide or semaglutide, require injections, which can be a barrier for some patients. Orforglipron works by mimicking the hormone GLP-1, which helps regulate appetite and glucose levels, but in a convenient pill form. Researchers are excited about its potential to simplify treatment and improve adherence, potentially leading to better outcomes for those struggling with obesity.

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

Research has shown that orforglipron, a pill mimicking a natural hormone, can aid weight loss in people with obesity. In earlier studies, participants taking orforglipron lost an average of 12.4% of their body weight over 72 weeks, compared to those on a placebo. This trial will provide participants with either orforglipron or a placebo. The treatment helps control hunger and blood sugar levels, promoting weight loss. Orforglipron also lowered A1C levels, which measure blood sugar control. These findings suggest it could be an effective option for managing obesity. ^{2 5 6 7 8}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 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 individuals who are overweight or have obesity with related health issues. It's designed to see if they can maintain weight loss after initial reduction. Specific eligibility details aren't provided, but typically participants must meet certain health criteria and not be taking conflicting medications.

Inclusion Criteria

Have completed the SURMOUNT-5 study on study treatment

Exclusion Criteria

I have hepatitis.

I have a history of pancreatitis.

I have a history of diabetes or severe diabetic complications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive orforglipron or placebo orally to evaluate the maintenance of body weight reduction

Duration not specified

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 study is testing the effectiveness of a drug called Orforglipron in helping people keep off weight they've already lost. Participants will either receive Orforglipron or a placebo (a substance with no active drug) to compare results.

How Is the Trial Designed?

Group I: Orforglipron Experimental Treatment 1 Intervention

Participants will receive orforglipron orally

Group II: Placebo Placebo Group 1 Intervention

Participants will receive placebo orally

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 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 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]

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 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]

Citations

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investor.lilly.com

investor.lilly.com/news-releases/news-release-details/lillys-oral-glp-1-orforglipron-demonstrated-statistically

Lilly's oral GLP-1, orforglipron, demonstrated statistically ...

Orforglipron is the first small molecule GLP-1 to successfully complete a Phase 3 trial, lowering A1C by an average of 1.3% to 1.6% across doses.

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06672939

NCT06672939 | A Study of Orforglipron (LY3502970) in ...

The main purpose of this study, performed under Master Protocol J4M-MC-PWMP, is to evaluate the efficacy, safety, and pharmacokinetics of orforglipron once ...

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; ...

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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 treatment showed similar or enhanced HbA1c reductions and weight loss ... 13 A study of LY3502970 in participants with obesity ...

5.

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.

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.

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.

8.

pnas.org

pnas.org/doi/10.1073/pnas.2014879117

Structural basis for GLP-1 receptor activation by ...

These head-to-head experiments with exenatide demonstrate that an orally administered nonpeptide agonist of the GLP-1R can reduce hyperglycemia ...