Orforglipron for Obesity

(ATTAIN-2 Trial)

No longer recruiting at 189 trial locations

Overseen By HARESH BOGHARA

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Must be taking: Oral antihyperglycemics

Must not be taking: DPP-4 inhibitors, GLP-1 agonists

Disqualifiers: Type 1 diabetes, 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: 22

Duration: 77 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of an oral medication called orforglipron to aid weight loss in people with obesity or overweight who also have type 2 diabetes. Participants will divide into groups to receive different doses of the medication or a placebo (a pill with no active medicine) over approximately 77 weeks. The trial is ideal for adults with a BMI of 27 or higher who have unsuccessfully tried dieting and have stable type 2 diabetes. 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 does not specify if you need to stop taking your current medications, but you must be on stable treatment for Type 2 Diabetes for at least 90 days before joining. You cannot be taking certain diabetes medications like DPP-4 inhibitors or GLP-1 receptor agonists.

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

Research shows that orforglipron is generally well-tolerated. One study completed a trial without major safety issues and reported a reduction in A1C levels (a measure of blood sugar control) by 1.3% to 1.6% with different doses. This suggests that orforglipron might be safe for individuals who are overweight or have obesity and type 2 diabetes.

Other studies indicate that orforglipron could be a safe treatment option taken once a day. As an oral medication, it is taken by mouth, unlike some treatments that require injections.

While most treatments can have some side effects, studies so far suggest that orforglipron is well-tolerated. Always consult a healthcare provider for personalized advice about joining a clinical trial. ^{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, unlike many current treatments that require injections, like semaglutide or liraglutide. This convenience of an oral medication could make it more appealing and accessible for patients. Additionally, Orforglipron acts as a GLP-1 receptor agonist, similar to some injectable options, but its oral administration could provide a more convenient alternative without compromising effectiveness. Researchers are excited about Orforglipron's potential to improve patient adherence and outcomes in managing obesity.

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

Research has shown that orforglipron, which participants in this trial may receive, can help adults with obesity lose weight. In one study, individuals taking orforglipron lost 12.4% of their body weight over 72 weeks, significantly outperforming those on a placebo (a pill with no active ingredient). This treatment affects the GLP-1 receptor, which helps control appetite and weight. Orforglipron is taken as a pill, offering a more convenient option compared to injections for some people. Overall, these results suggest that orforglipron could be a promising choice for managing weight. ^{1 4 6 7 8}

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?

Adults with obesity or overweight and type 2 diabetes are eligible for this trial. They must have tried to lose weight through dieting without success, have stable blood sugar levels on up to three oral diabetes medications (excluding certain types), and a BMI of at least 27.0 kg/m². Those with recent significant weight changes, Type 1 Diabetes, diabetic eye treatment plans, or a history/family history of specific thyroid cancers cannot participate.

Inclusion Criteria

I have Type 2 Diabetes with an HbA1c level between 7% and 10%, and have been on a stable treatment for at least 90 days.

I have Type 2 Diabetes with an HbA1c level between 7% and 10%, and have been on a stable treatment plan for at least 90 days.

You need to have a body mass index (BMI) of 27 or higher.

Exclusion Criteria

I have a history of pancreatitis.

I or a close family member have had medullary thyroid cancer or MEN2.

I am currently getting or planning to get treatment for eye problems related to diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive once daily oral treatment with orforglipron or placebo

77 weeks

Up to 22 visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Orforglipron
• Placebo

Trial Overview The study is testing the safety and effectiveness of Orforglipron, an oral medication taken once daily for reducing body weight in adults with obesity/overweight and type 2 diabetes. Participants will be randomly assigned to receive either Orforglipron or a placebo over approximately 77 weeks with up to 22 visits.

How Is the Trial Designed?

Group I: Orforglipron Dose 3 Experimental Treatment 1 Intervention

Participants will receive orforglipron administered orally.

Group II: Orforglipron Dose 2 Experimental Treatment 1 Intervention

Participants will receive orforglipron administered orally.

Group III: Orforglipron Dose 1 Experimental Treatment 1 Intervention

Participants will receive orforglipron administered orally.

Group IV: Placebo Placebo Group 1 Intervention

Participants will receive placebo

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. 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.

4. 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 ...

5. 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 ...

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

Orforglipron (LY3502970), a novel, oral non-peptide ... Aim: To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple doses of orforglipron (LY3502970), ...

7. 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.

8. 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 ...