Orforglipron for Obesity

No longer recruiting at 3 trial locations

Overseen By There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Eli Lilly and Company

Must not be taking: Weight loss medications

Disqualifiers: Diabetes, Unstable weight, Hepatitis, others

Compensation: Varies

Number of Visits: Unknown

Duration: 8 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called orforglipron, a potential weight loss drug, to determine its effectiveness in reducing body fat in individuals with obesity or who are overweight. Participants will receive either orforglipron or a placebo (a pill with no active drug) for about 8 months. It is suitable for individuals with a Body Mass Index (BMI) of 30 or more, or 27 or more with additional health issues, who are not currently using weight loss medications or have diabetes. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop taking my current medications for the trial?

The trial requires that you stop taking any medications or alternative remedies used to manage weight loss.

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

Research has shown that orforglipron, a pill for treating obesity, has undergone safety testing in people. In one study, adults with obesity took doses of 6 mg, 12 mg, and 36 mg of orforglipron. The study found the treatment to be generally safe and well-tolerated.

Another study found that orforglipron significantly reduced blood sugar levels and body weight, with no major safety issues reported. These results suggest that orforglipron is generally safe, though it might have side effects. Participants in the studies did not report any unusual or severe reactions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Orforglipron because it offers a new approach to treating obesity. Unlike current treatments that often involve injectable medications or surgeries, Orforglipron is taken orally, making it much more convenient for patients. Most existing obesity treatments focus on suppressing appetite or altering metabolism, but Orforglipron works as a small molecule GLP-1 receptor agonist, which may provide an effective and novel mechanism of action. This could lead to significant weight loss with potentially fewer side effects, making it a promising option for people struggling with obesity.

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

Research has shown that orforglipron, which participants in this trial may receive, helps people with obesity lose weight. In studies, those taking orforglipron lost significantly more weight than those taking a placebo, a pill with no active ingredients. Over 72 weeks, individuals on orforglipron lost between 7.8% and 12.4% of their starting weight, depending on the dose. Most of this weight loss came from body fat, with 73.1% of the reduction being fat. At the highest dose, participants lost an average of 16 pounds. These findings suggest that orforglipron could be a promising option for reducing body fat. ^{1 2 3 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 adults with obesity or overweight who are interested in testing a new drug, Orforglipron. Participants will be involved in the study for about 8 months.

Inclusion Criteria

Have a Body Mass Index (BMI) of ≥30.0 kilograms per square meter (kg/m2)

Have a Body Mass Index (BMI) of ≥27.0 kg/m2 with comorbidities

Exclusion Criteria

Have an unstable body weight within 90 days prior to screening

I am using medication or remedies for weight loss.

I have diabetes and/or a history of 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 assess the effect on body composition

8 months

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 aims to compare the effects of a new medication called Orforglipron against a placebo (a substance with no active drug) on reducing body fat in obese or overweight individuals.

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

A study involving over 28,000 patients found that orlistat and sibutramine have different safety profiles, with orlistat primarily causing gastrointestinal issues like diarrhea, while sibutramine was associated with central nervous system effects and hypertension.

The findings from prescription-event monitoring (PEM) were consistent with published case reports, confirming that the adverse events linked to these medications align with their distinct mechanisms of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety profiles of orlistat and sibutramine: results of prescription-event monitoring studies in England. Perrio, MJ., Wilton, LV., Shakir, SA.[2021]

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 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]

Modest weight loss of about 5% through dietary changes and increased activity can significantly reduce the risk of obesity-related diseases and delay the onset of type 2 diabetes in patients with a BMI of 27 or higher.

Weight loss medications can enhance adherence to lifestyle changes and lead to meaningful improvements in health outcomes, but careful selection and understanding of the benefits and risks of these medications are essential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical effectiveness of weight loss drugs. Wittert, G., Caterson, I., Finer, N.[2014]

Citations

1.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2511774

Orforglipron, an Oral Small-Molecule GLP-1 Receptor ...

In the pooled orforglipron groups, 73.1% of the body-weight reduction was due to a loss in fat mass and 26.9% was due to a loss in lean mass.

2.

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 ...

In an additional key secondary endpoint, participants taking orforglipron lost an average of 16.0 lbs (7.9%) at the highest dose. Given that ...

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.

news.weill.cornell.edu

news.weill.cornell.edu/news/2025/09/oral-glp-1-drug-orforglipron-promotes-substantial-weight-loss-in-clinical-trial

Oral GLP-1 Drug Orforglipron Promotes Substantial Weight ...

Over 72 weeks, patients in the low-, medium- and high-dose orforglipron groups lost an average of 7.8%, 9.3% and 12.4% of their initial body ...

5.

nature.com

nature.com/articles/d41591-025-00060-6

New GLP-1 drug delivers weight loss in a pill

Orforglipron resulted in significantly greater weight loss than placebo. After 72 weeks, mean weight reduction from baseline was –7.5% (6 mg ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05869903

NCT05869903 | A Study of Orforglipron (LY3502970) in ...

This study will investigate the efficacy and safety of once daily oral orforglipron in adult participants with obesity or overweight with weight-related ...

7.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0140673623013028

Efficacy and safety of oral orforglipron in patients with type ...

The novel, oral, non-peptide GLP-1 receptor agonist orforglipron at doses of 12 mg or greater showed significant reductions in HbA 1c and bodyweight compared ...