Orforglipron for Obesity

(ATTAIN-OA PAIN Trial)

Recruiting at 92 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

Must not be taking: GLP-1 receptor agonists

Disqualifiers: Diabetes, Recent heart condition, 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

800 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the efficacy and safety of orforglipron, a new potential drug, for individuals who are overweight or have obesity and suffer from knee osteoarthritis with pain. Participants will receive either orforglipron or a placebo to compare outcomes. The study seeks individuals with a BMI of 27 or higher, who have unsuccessfully attempted weight loss through diet, and experience knee osteoarthritis symptoms such as morning stiffness or a grinding sensation in the knee. The trial will last approximately 74 weeks. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have used any GLP-1 receptor agonist medication within 180 days before screening.

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

Research has shown that orforglipron appears safe for people with obesity. Earlier studies explored its use for weight loss and found it well-tolerated. Participants lost weight, indicating the treatment's effectiveness, and no major safety issues were reported.

Regarding side effects, data from previous trials do not reveal any significant safety concerns. This is encouraging, especially since the treatment is now in a later stage of testing, which usually indicates it has proven safe in earlier studies. Additionally, orforglipron is being tested for other conditions, like diabetes, further supporting its safety. ^{1 2 3 4 5}

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

Orforglipron is unique because it offers a new oral treatment option for obesity, potentially simplifying the regimen compared to current injectable therapies like semaglutide and liraglutide. Unlike these standard treatments, orforglipron targets obesity through a novel mechanism by acting as a non-peptide glucagon-like peptide-1 (GLP-1) receptor agonist. Researchers are excited about orforglipron because it might provide similar or improved weight loss benefits without the need for injections, making it more convenient for patients.

What evidence suggests that orforglipron could be an effective treatment for obesity and knee osteoarthritis?

Research has shown that orforglipron aids in weight loss. In earlier studies, participants taking orforglipron lost between 7.8% and 12.4% of their starting weight over 72 weeks. Another study found that participants lost an average of 16 pounds with the highest dose, with most weight loss coming from fat reduction. In this trial, participants will receive either orforglipron or a placebo. Previous research indicates that orforglipron results in significantly more weight loss compared to a placebo. ^{1 2 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 with obesity or overweight who also have knee osteoarthritis and pain. Participants will be involved in the study for approximately 74 weeks.

Inclusion Criteria

Have a body mass index (BMI) of 27 kilograms per square meter (kg/m2) or higher at screening

Have tried at least once to lose weight through diet but were unsuccessful

I am over 50, have knee stiffness in the morning, or my knee makes a crackling sound.

Exclusion Criteria

Have gained or lost more than 11 pounds within 90 days prior to screening

I have had or plan to have weight loss surgery within 18 months.

I currently have a knee infection.

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 efficacy and safety in treating obesity or overweight with osteoarthritis of the knee

72 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Orforglipron

Trial Overview The trial is testing Orforglipron, a new potential treatment, against a placebo to see how well it works and its safety in people with both obesity or overweight and knee osteoarthritis.

How Is the Trial Designed?

Group I: Orforglipron (GZT2) Experimental Treatment 1 Intervention

Participants will receive orforglipron orally

Group II: Orforglipron (GZT1) Experimental Treatment 1 Intervention

Participants will receive orforglipron orally

Group III: Placebo (GZT1) Placebo Group 1 Intervention

Participants will receive placebo orally

Group IV: Placebo (GZT2) 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

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 ... 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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37852529/

Safety and efficacy of the new, oral, small-molecule, GLP-1 ... Preliminary evidence supports that orforglipron and danuglipron are efficient in glycemic control and weight reduction in T2DM, obesity or both.

7. 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 ...

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa2302392

Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults ... This phase 2 trial of orforglipron showed weight reduction ranging from 8.6% to 12.6% at 26 weeks and ranging from 9.4% to 14.7% at 36 weeks.