Orforglipron for Type 2 Diabetes

(ACHIEVE-5 Trial)

No longer recruiting at 81 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests orforglipron, a new oral treatment, to determine its effectiveness for people with Type 2 Diabetes (T2D) who struggle to control their blood sugar with current insulin treatments. Researchers aim to assess the safety and efficacy of orforglipron by comparing different doses against a placebo (a harmless pill with no active drug). Suitable participants have T2D, face challenges with blood sugar control despite using insulin glargine, and have maintained a stable treatment plan for at least 90 days. The study spans about 46 weeks and may involve up to 20 visits to monitor progress. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking diabetes treatment.

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.

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

Research shows that orforglipron, a pill for type 2 diabetes, has undergone testing for safety and tolerability. In earlier studies, 86.3% of participants taking orforglipron experienced side effects, which are any unwanted effects after taking the treatment. These findings indicate that while side effects exist, further research aims to understand them better. The advanced stage of this trial suggests that earlier studies have already provided some evidence of safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Type 2 Diabetes?

Orforglipron is unique because it is an oral medication designed for treating Type 2 Diabetes, unlike many current treatments that often require injections, like insulin or GLP-1 receptor agonists. Researchers are excited about Orforglipron because it offers a new and potentially more convenient way to manage blood sugar levels without the need for needles. Additionally, Orforglipron works by mimicking the action of the hormone GLP-1, which helps to regulate insulin and glucose in the body, potentially providing effective control over diabetes with fewer side effects.

What evidence suggests that orforglipron might be an effective treatment for Type 2 Diabetes?

Research has shown that orforglipron, which participants in this trial may receive, effectively lowers blood sugar in people with early type 2 diabetes. One study found that participants taking orforglipron experienced a significant drop in their average blood sugar levels over 40 weeks. This average is measured by glycated hemoglobin, which reflects blood sugar levels over a few months. Orforglipron works by activating certain receptors in the body that help reduce blood sugar. Current evidence suggests that orforglipron can achieve similar results to some injectable diabetes treatments, but it comes in an easy-to-take pill form. ^{1 3 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?

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 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 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]

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]

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 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]

Citations

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

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.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05803421

NCT05803421 | A Study of Daily Oral Orforglipron ... The main purpose of this study is to determine safety and efficacy of orforglipron compared with insulin glargine in participants with type 2 diabetes and ...

3. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/dom.15150

Orforglipron (LY3502970), a novel, oral non‐peptide glucagon ... The current data show this non-peptide agonist has the potential to achieve a similar efficacy to that of some injectable GLP-1RAs, while ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7703558/

Structural basis for GLP-1 receptor activation by ... In efficacy studies, oral administration of LY3502970 resulted in glucose lowering in humanized GLP-1R transgenic mice and insulinotropic and ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05971940

NCT05971940 | A Study of Orforglipron (LY3502970) in ... The main purpose of this study is to determine safety and efficacy of orforglipron compared with placebo in adult participants with type 2 diabetes and ...

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. pnas.org pnas.org/doi/10.1073/pnas.2014879117

Structural basis for GLP-1 receptor activation by ... Therapeutically, the GLP-1 mimetic exenatide was the first GLP-1R agonist approved for the treatment of type 2 diabetes mellitus (T2DM) (4, 5).

8. delta.larvol.com delta.larvol.com/Products/?ProductId=66263e96-ea3d-4d35-bc39-0de9a77ab272

orforglipron (OWL833) / Roche, Eli Lilly - "Lilly plans to submit orforglipron for the treatment of type 2 diabetes to global regulatory agencies in 2026". Filing • P3 data • Type 2 Diabetes Mellitus.