Orforglipron for Type 2 Diabetes

(ACHIEVE-5 Trial)

Recruiting at 77 trial locations

Overseen By Joseph Soufer

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Must be taking: Insulin glargine

Disqualifiers: Heart failure, Stroke, Hepatitis, 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: 20

Duration: 46 weeks

520 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The main purpose of this study is to determine the safety and efficacy of orforglipron. Participants will have Type 2 Diabetes (T2D) and have inadequate glycemic control with insulin glargine with or without metformin and/or SGLT-2 (sodium-glucose cotransporter-2) inhibitor. The study will last about 46 weeks and may include up to 20 visits.

Do I have to stop taking my current medications for this trial?

No, you don't have to stop taking your current medications. The trial requires that you continue with your stable doses of insulin glargine, metformin, and/or SGLT-2 inhibitors if you are already on them.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should have been on stable doses of insulin glargine, metformin, and/or SGLT-2 inhibitors for at least 90 days before starting the trial.

What safety data is available for Orforglipron in treating Type 2 Diabetes?

Safety data for Orforglipron, also known as LY3502970, has been evaluated in several studies. A Phase 1b trial assessed its safety, pharmacokinetics, and pharmacodynamics in patients with Type 2 Diabetes, while a Phase 2 study compared its safety and efficacy against placebo and dulaglutide. Additionally, a Phase 1a study evaluated its safety and tolerability in healthy participants. These studies indicate that Orforglipron has been tested for safety in both diabetic and healthy individuals. ^{1 2 3 4 5}

Is Orforglipron safe for humans?

Orforglipron has been tested in several studies for safety in people with type 2 diabetes and obesity. These studies generally found it to be safe, with some participants experiencing mild side effects similar to those of other medications in its class. ^{1 2 3 4 5}

Is the drug Orforglipron a promising treatment for Type 2 Diabetes?

Yes, Orforglipron is a promising drug for Type 2 Diabetes. It is an oral medication that helps control blood sugar levels by mimicking a natural hormone in the body. It has shown positive results in clinical trials, helping people with Type 2 Diabetes manage their condition effectively. ^{1 2 4 6 7}

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

Orforglipron is unique because it is an oral, non-peptide drug that mimics the action of a natural hormone (GLP-1) to help control blood sugar levels, unlike many other treatments that are injectable. ^{1 2 4 6 7}

What data supports the idea that Orforglipron for Type 2 Diabetes is an effective drug?

The available research shows that Orforglipron is effective for treating Type 2 Diabetes. In a study comparing Orforglipron to a placebo and another diabetes drug called dulaglutide, Orforglipron showed positive results. This means that people taking Orforglipron had better outcomes than those taking a placebo, and it was comparable to dulaglutide, which is already used to treat diabetes. Additionally, Orforglipron has been shown to help with weight loss in people with obesity, which is often a related issue for those with Type 2 Diabetes. ^{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 taken by mouth, helps people with type 2 diabetes by acting on a specific receptor in the body to improve blood sugar control. It has also been shown to help with weight loss in people with obesity, which is often a related condition. ^{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?

This trial is for adults with Type 2 Diabetes who haven't been able to control their blood sugar levels using insulin glargine, possibly alongside metformin or SGLT-2 inhibitors. They should have had a stable dose of insulin and body weight for the past 90 days and an HbA1c level between 7.0% to 10.5%. People with a history of pancreatitis, liver diseases other than fatty liver, severe heart failure, or recent major cardiovascular events cannot participate.

Inclusion Criteria

I have been on a stable dose of insulin glargine U-100 for over 90 days.

Your HbA1c levels are between 7.0% and 10.5%.

I have been on a stable dose of insulin glargine U-100 for at least 90 days.

Exclusion Criteria

Are you currently enrolled in another study?

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

46 weeks

Up to 20 visits

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 tests the safety and effectiveness of Orforglipron in managing blood sugar in people with Type 2 Diabetes over approximately 46 weeks and up to 20 visits. Participants will be randomly assigned to receive either Orforglipron or a placebo while continuing their current diabetes medications.

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 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]

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 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]

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]

GLP-1 receptor agonists, like liraglutide, not only help manage type 2 diabetes by stimulating insulin release and inhibiting glucagon but also promote weight loss, leading to their approval for weight management.

These medications have additional nonglycemic effects on various body systems, including cardiovascular, neurological, and renal functions, which could be beneficial for patients beyond just weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GLP-1 receptor agonists: Nonglycemic clinical effects in weight loss and beyond. Ryan, D., Acosta, A.[2018]

Citations

1. 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]

2. 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]

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

In obesity or overweight without diabetes, orforglipron increased weight loss at 26 wk. [2023]

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

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

5. England 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. [2022]

6. 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]

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

GLP-1 receptor agonists: Nonglycemic clinical effects in weight loss and beyond. [2018]