Orforglipron for Type 2 Diabetes and Obesity

(ACHIEVE-4 Trial)

Recruiting at 469 trial locations

Overseen By Joseph Soufer

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Must be taking: Oral antihyperglycemics

Must not be taking: Weight loss drugs

Disqualifiers: Type 1 diabetes, Pancreatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 27

Duration: 104 weeks

2749 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but you must be on a stable treatment of 1 to 3 specific diabetes drugs (metformin, SGLT-2 inhibitors, and/or sulfonylureas) for at least 90 days before joining.

What data supports the effectiveness of the drug Orforglipron for Type 2 Diabetes and Obesity?

Research shows that Orforglipron, a GLP-1 receptor agonist (a type of drug that helps control blood sugar and may aid weight loss), is effective in managing type 2 diabetes and obesity. Similar drugs in this class have been shown to help with weight loss and blood sugar control, supporting Orforglipron's potential effectiveness. ^{1 2 3 4 5}

What makes the drug Orforglipron unique for treating type 2 diabetes and obesity?

Orforglipron is unique because it is an oral, non-peptide GLP-1 receptor agonist, which means it can be taken as a pill rather than an injection, making it more convenient for patients with type 2 diabetes and obesity. ^{1 3 4 6 7}

What is the purpose of this trial?

This trial is testing a new diabetes medication called orforglipron to see if it is safer and more effective than insulin in people with type 2 diabetes who are overweight or obese and at higher risk for heart problems. The study will last several years and involve multiple visits.

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

Eligibility Criteria

This trial is for adults with type 2 diabetes and obesity or overweight, who also have a higher risk of heart disease. Participants should not be on insulin therapy but may be taking other diabetes medications.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either orforglipron or insulin glargine for the duration of the study

104 weeks

Up to 27 visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Insulin Glargine
• Orforglipron

Trial Overview The study tests the safety and effectiveness of a daily oral medication called Orforglipron compared to Insulin Glargine, an injectable insulin, over about two years with up to 27 visits.

Participant Groups

Group I: Orforglipron Experimental Treatment 1 Intervention

Participants will receive escalated doses of orforglipron orally.

Group II: Insulin Glargine Active Control 1 Intervention

Participants will receive insulin glargine subcutaneously (SC). Doses will be individualized and titrated according to a treat-to-target algorithm.

Insulin Glargine is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Lantus for:

• Type 1 diabetes
• Type 2 diabetes

Approved in United States as Lantus for:

• Type 1 diabetes
• Type 2 diabetes

Approved in Canada as Lantus for:

• Type 1 diabetes
• Type 2 diabetes

Approved in Japan as Lantus for:

• Type 1 diabetes
• Type 2 diabetes

Approved in China as Lantus for:

• Type 1 diabetes
• Type 2 diabetes

Approved in Switzerland as Lantus for:

• Type 1 diabetes
• Type 2 diabetes

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

Findings from Research

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]

GLP-1 receptor agonists, while effective in reducing weight and postprandial blood glucose levels, do not significantly lower HbA1c levels compared to insulin glargine, indicating similar efficacy in glycemic control.

Insulin glargine was found to be more effective in reducing fasting blood glucose but was associated with a higher incidence of nocturnal hypoglycemia and influenza, while GLP-1 receptor agonists had more gastrointestinal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide-1 receptor agonists versus insulin glargine for type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials. Li, WX., Gou, JF., Tian, JH., et al.[2021]

In a 24-week phase III study involving 756 patients with type 2 diabetes, LY2963016 insulin glargine (LY IGlar) demonstrated non-inferiority to the reference product Lantus(®) (IGlar) in reducing HbA1c levels, indicating it is equally effective for glucose control.

Both LY IGlar and IGlar had similar safety profiles, with no significant differences in adverse events, weight change, or hypoglycemia, suggesting that LY IGlar is a safe alternative to IGlar for patients with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Similar efficacy and safety of LY2963016 insulin glargine and insulin glargine (Lantus®) in patients with type 2 diabetes who were insulin-naïve or previously treated with insulin glargine: a randomized, double-blind controlled trial (the ELEMENT 2 study). Rosenstock, J., Hollander, P., Bhargava, A., 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]

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 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]

References

1. 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]

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

Glucagon-like peptide-1 receptor agonists versus insulin glargine for type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials. [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Lilly Insulin Glargine Versus Lantus® in Type 2 Diabetes Mellitus Patients: India and East Asia Subpopulation Analyses of the ELEMENT 5 Study. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Similar efficacy and safety of LY2963016 insulin glargine and insulin glargine (Lantus®) in patients with type 2 diabetes who were insulin-naïve or previously treated with insulin glargine: a randomized, double-blind controlled trial (the ELEMENT 2 study). [2022]

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

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

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

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

7. 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]