Orforglipron for Type 2 Diabetes

(ACHIEVE-1 Trial)

No longer recruiting at 117 trial locations

Overseen By Robert Noveck

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Must not be taking: Insulin, Antihyperglycemics

Disqualifiers: Type 1 diabetes, Heart failure, 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: 54 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates how well a new treatment, orforglipron, works for people with type 2 diabetes who can't control their blood sugar with just diet and exercise. It compares different doses of orforglipron to a placebo (a pill with no active medicine) over about a year. Suitable participants have type 2 diabetes, struggle to control their blood sugar, and haven't used insulin recently. 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.

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

The trial requires that you have not used any oral or injectable diabetes medications in the 90 days before screening, so you may need to stop taking those if you are currently using them.

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

Research shows that orforglipron is generally safe for use. In earlier studies, patients taking orforglipron achieved better blood sugar control without major safety issues. Specifically, the drug reduced A1C levels, a measure of blood sugar control, by an average of 1.3% to 1.6% at different doses.

Orforglipron has also been tested for conditions like obesity and high blood pressure, indicating broad safety. This treatment is currently in a Phase 3 trial, meaning earlier stages have already assessed its safety. While all medications can have side effects, evidence so far suggests that orforglipron is promising and safe for many people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about orforglipron for Type 2 Diabetes because it offers a novel approach compared to current treatments. Unlike many standard medications that are injectable, orforglipron is taken orally, making it more convenient for patients. Additionally, it belongs to a class of drugs known as GLP-1 receptor agonists, but it is non-peptide, which could lead to better stability and absorption in the body. These features could potentially improve patient adherence and outcomes, making orforglipron a promising new option in diabetes care.

What evidence suggests that orforglipron might be an effective treatment for type 2 diabetes?

Research has shown that orforglipron holds promise for treating type 2 diabetes. In studies, over 65% of participants taking the highest dose achieved an A1C level of 6.5% or lower, a key measure of blood sugar. This trial will test different doses of orforglipron—Dose 1, Dose 2, and Dose 3—to evaluate their effectiveness. Another study found that orforglipron significantly lowered blood sugar levels over 40 weeks. It also resulted in noticeable weight loss and improved blood sugar control compared to a placebo. These findings suggest that orforglipron could effectively help those struggling to manage blood sugar with diet and exercise alone. ^{1 2 5 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?

Adults with Type 2 Diabetes who haven't been able to control their blood sugar levels through diet and exercise alone can join. They should have a stable weight, a BMI of at least 23, and an HbA1c level between 7.0% to 9.5%. Participants shouldn't be on insulin or other diabetes medications for the last 90 days.

Inclusion Criteria

My weight has been stable for the last 3 months, and I won't start a strict diet or exercise program during the study.

Your blood sugar levels, measured by a lab test, are too high even though you have been trying to control them with diet and exercise.

I haven't used diabetes medication for 90 days, except for short-term insulin.

Exclusion Criteria

I have severe heart failure.

I am being treated or will be treated for diabetic eye problems.

I have not had ketoacidosis or a hyperosmolar coma in the last 6 months.

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

54 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Forglipron

Trial Overview The trial is testing Orforglipron against a placebo in adults with Type 2 Diabetes over approximately one year. The goal is to see if Orforglipron is safe and more effective than no treatment (placebo) in controlling blood sugar levels.

How Is the Trial Designed?

Group I: Orforglipron Dose 3 Experimental Treatment 1 Intervention

Participants will receive orforglipron orally.

Group II: Orforglipron Dose 2 Experimental Treatment 1 Intervention

Participants will receive orforglipron orally.

Group III: Orforglipron Dose 1 Experimental Treatment 1 Intervention

Participants will receive orforglipron orally.

Group IV: 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 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]

The review highlights that while there are many innovative drugs being developed for type 2 diabetes, several have faced serious safety issues, leading to their withdrawal or halting of development.

It discusses the current state of treatments, including glitazones, incretin mimetics, SGLT-2 inhibitors, and new experimental drugs, emphasizing the need for better methods to predict and differentiate drug-related adverse events from natural disease occurrences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Benefits and risks of current pharmacotherapy in the treatment of type 2 diabetes]. Schindler, C., Barthel, A., Fischer, S., et al.[2021]

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 1 study involving 92 healthy adults, orforglipron (LY3502970) demonstrated a favorable safety profile, with gastrointestinal issues being the most common side effects, and showed a long half-life of 25-68 hours, allowing for convenient once-daily oral dosing.

Participants taking orforglipron experienced significant weight loss (up to 5.4 kg) and reductions in fasting glucose levels over 4 weeks, indicating its potential efficacy as a glucagon-like peptide-1 receptor agonist for managing weight and blood sugar.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Orforglipron (LY3502970), a novel, oral non-peptide glucagon-like peptide-1 receptor agonist: A Phase 1a, blinded, placebo-controlled, randomized, single- and multiple-ascending-dose study in healthy participants. Pratt, E., Ma, X., Liu, R., et al.[2023]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2505669

Orforglipron, an Oral Small-Molecule GLP-1 Receptor ... In adults with early type 2 diabetes, orforglipron significantly reduced the glycated hemoglobin level over a period of 40 weeks. (Supported by ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40544435/

Orforglipron, an Oral Small-Molecule GLP-1 Receptor ... Conclusions: In adults with early type 2 diabetes, orforglipron significantly reduced the glycated hemoglobin level over a period of 40 weeks. ...

3. appliedclinicaltrialsonline.com appliedclinicaltrialsonline.com/view/eli-lilly-orforglipron-superior-efficacy-multiple-trials-type-2-diabetes

Eli Lilly's Orforglipron Shows Superior Efficacy Across ... Orforglipron met primary and secondary endpoints in Phase III trials, showing significant A1C reduction and weight loss in type 2 diabetes ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37369232/

Efficacy and safety of oral orforglipron in patients with type ... HbA1c reduction was statistically superior with orforglipron versus placebo (estimated treatment difference -0·8% to -1·7%). Change in mean ...

5. 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 a key secondary endpoint, more than 65% of participants taking the highest dose of orforglipron achieved an A1C less than or equal to 6.5%, ...

6. nejm.org nejm.org/doi/full/10.1056/NEJMoa2511774

Orforglipron, an Oral Small-Molecule GLP-1 Receptor ... This drug is in clinical development for obesity as well as for type 2 diabetes, hypertension, osteoarthritis, and obstructive sleep apnea. We ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06010004

NCT06010004 | A Long-term Safety Study of Orforglipron ( ... The purpose of this study is to determine the long-term safety of the study intervention orforglipron as a monotherapy or in combination with oral ...