Orforglipron for Type 2 Diabetes

(ACHIEVE-1 Trial)

Recruiting at 113 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

559 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a new medication called orforglipron to help adults with type 2 diabetes who can't control their blood sugar with diet and exercise alone. The medication aims to improve how the body manages sugar levels.

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 orforglipron safe for humans?

Orforglipron has been studied for safety in people with type 2 diabetes and obesity. Research shows it is generally safe, but like any medication, it may have side effects. Always discuss with your doctor before starting any new treatment. ^{1 2 3 4 5}

How is the drug orforglipron different from other treatments for type 2 diabetes?

Orforglipron is unique because it is an oral medication that acts as a glucagon-like peptide-1 (GLP-1) receptor agonist, which is typically available as an injection. This makes it more convenient for people who prefer not to use injections. ^{1 2 3 4 6}

What data supports the effectiveness of the drug Orforglipron for treating type 2 diabetes?

Research shows that Orforglipron, a drug that helps control blood sugar by mimicking a natural hormone in the body, has been effective in treating type 2 diabetes and obesity. Studies have compared it to other treatments and found it to be safe and effective in managing these conditions. ^{1 2 3 4 6}

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 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]

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]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Safety and efficacy of the new, oral, small-molecule, GLP-1 receptor agonists orforglipron and danuglipron for the treatment of type 2 diabetes and obesity: systematic review and meta-analysis of randomized controlled trials. [2023]

3. England 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. [2023]

4. England 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. [2023]

5. England 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. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

[Benefits and risks of current pharmacotherapy in the treatment of type 2 diabetes]. [2021]