Orforglipron for Obesity

Recruiting at 51 trial locations

Overseen By Physicians interested in becoming principal investigators please contact

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Disqualifiers: Prepubertal, Type 1 diabetes, 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: 72 weeks

125 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called orforglipron (a GLP-1 receptor agonist) to determine its effectiveness for teens with obesity or those who are overweight with related health issues like high blood pressure or type 2 diabetes. Participants will take either orforglipron or a placebo (a sugar pill with no active medicine) to compare results. The trial aims to evaluate the treatment's safety and effectiveness over approximately 18 months. It is suitable for teens who have struggled to lose weight despite trying diet and exercise plans. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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 shows that orforglipron, a pill, has a safety profile similar to other injectable medications used for diabetes and obesity. Studies indicate that orforglipron is generally well-tolerated, with most people not experiencing serious side effects. Common issues may include mild symptoms like an upset stomach, similar to other treatments in this category.

Since this study is in a later phase, there is already some confidence in its safety for humans. Earlier phases focus heavily on safety, so by this point, researchers have a good understanding of how people respond to the treatment. This suggests that the treatment is fairly safe for human use, based on previous research and testing. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for obesity?

Researchers are excited about Orforglipron for obesity because it offers a fresh approach compared to existing treatments like lifestyle changes, medications such as orlistat, or injectable GLP-1 agonists. Unlike most treatments, Orforglipron is taken orally, making it potentially more convenient for patients who prefer not to take injections. Additionally, it acts as a non-peptide GLP-1 receptor agonist, which is a newer mechanism in obesity treatment that might offer effective weight management with fewer side effects. This novel mechanism and delivery method could make it a game-changer in the fight against obesity.

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

Studies have shown that orforglipron, an oral medication, can help individuals with obesity lose a significant amount of weight. In this trial, participants will receive either orforglipron or a placebo. Research indicates that adults who took orforglipron lost about 12.4% of their body weight after 72 weeks, surpassing those who took a placebo (a pill with no active ingredient). Orforglipron mimics a hormone that regulates hunger and blood sugar levels. In addition to weight loss, participants who took orforglipron experienced improved blood sugar control. These findings suggest that orforglipron 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?

Adolescents with obesity, or overweight with related health issues like hypertension or type 2 diabetes, who've tried losing weight through diet and exercise without success. They must have a BMI in the top percentiles for their age and sex. Those who've lost significant weight recently, plan to undergo bariatric surgery, or have conditions causing secondary obesity can't participate.

Inclusion Criteria

I tried and failed to lose enough weight with a diet and exercise program for 3 months.

I am overweight or obese according to CDC guidelines and have a related health issue.

Exclusion Criteria

I or my family have a history of medullary thyroid cancer or MEN2.

Have HbA1c >9.0% (75 mmol/mol) as measured by central laboratory at screening

I have not started puberty.

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 once daily

72 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 trial is testing Orforglipron against a placebo to see if it helps adolescents lose weight safely over an 18-month period. It will also look at how the body processes the drug.

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 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]

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]

Citations

1. 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; ...

4. 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 ...