Orforglipron vs Semaglutide for Type 2 Diabetes

(ACHIEVE-3 Trial)

Recruiting at 159 trial locations

Overseen By Chad Crystal

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Must be taking: Metformin

Disqualifiers: Type 1 diabetes, Heart failure, 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: Unknown

Duration: 61 weeks

1576 Participants Needed

Trial Summary

What is the purpose of this trial?

The main purpose of this study is to assess efficacy and safety of orforglipron compared with oral semaglutide in participants with Type 2 diabetes and inadequate glycemic control with metformin.The study will last around 61 weeks.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must continue taking metformin at a stable dose if you are already on it.

What data supports the effectiveness of the drug Orforglipron vs Semaglutide for Type 2 Diabetes?

Semaglutide, a drug similar to Orforglipron, has been shown to effectively lower blood sugar levels and promote weight loss in people with type 2 diabetes. It works by stimulating insulin release and has been proven effective in various clinical trials. ^{1 2 3 4 5}

Is Orforglipron or Semaglutide safe for humans?

Both Orforglipron and Semaglutide have been evaluated for safety in clinical trials for type 2 diabetes. Orforglipron has undergone Phase 1b and Phase 2 studies, while Semaglutide has been tested in multiple Phase III trials, showing a good safety profile in patients with type 2 diabetes. ^{1 2 3 6 7}

How does the drug Orforglipron differ from other treatments for type 2 diabetes?

Orforglipron is unique because it is an oral, non-peptide drug that activates the glucagon-like peptide-1 receptor, unlike many other treatments that require injection. This makes it more convenient for patients who prefer not to use injections. ^{1 2 3 6 7}

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 who have been taking metformin consistently and haven't achieved desired blood sugar control. Participants should not have had any significant weight changes or started new diets or intense exercise programs recently. They can't join if they have Type 1 Diabetes, recent severe diabetes complications, certain cancers, high serum calcitonin levels, advanced heart failure, are undergoing treatment for diabetic eye disease, or have severely reduced kidney function.

Inclusion Criteria

I have been taking at least 1500 mg of metformin daily for the last 90 days.

Your long-term blood sugar level (HbA1c) is between 7.0% and 10.5%.

I have Type 2 Diabetes.

Exclusion Criteria

I am getting or planning to get treatment for eye problems related to diabetes.

I have been cancer-free or in remission for less than 5 years.

I have had a severe diabetic complication in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either orforglipron or semaglutide orally to assess efficacy and safety

61 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Orforglipron
• Semaglutide

Trial Overview The study compares the effectiveness and safety of a new medication called Orforglipron to an existing drug named Semaglutide in managing blood sugar levels over approximately 61 weeks in people whose Type 2 Diabetes isn't well-controlled by metformin alone.

Participant Groups

Group I: Orforglipron Dose 2 Experimental Treatment 1 Intervention

Participants will receive orforglipron orally.

Group II: Orforglipron Dose 1 Experimental Treatment 1 Intervention

Participants will receive orforglipron orally.

Group III: Semaglutide Dose 1 Active Control 1 Intervention

Participants will receive semaglutide orally.

Group IV: Semaglutide Dose 2 Active Control 1 Intervention

Participants will receive semaglutide 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

Findings from Research

Semaglutide, a GLP-1 receptor agonist with a long half-life, effectively promotes insulin secretion in a glucose-dependent manner, making it a valuable treatment for type 2 diabetes, approved for use worldwide and in Japan since 2018.

Oral semaglutide (Rybelsus®) is the first GLP-1 receptor agonist available in pill form, showing continuous benefits in glycemic control for patients with type 2 diabetes across various stages, as demonstrated in multiple global clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New drug for type 2 diabetes: introduction of oral Semaglutide (Rybelsus® tablets), an oral GLP-1 receptor agonist]. Miyasaka, K.[2022]

Semaglutide (Ozempic®) is an effective once-weekly treatment for type 2 diabetes, showing superior glucose-lowering effects and greater weight loss compared to other GLP-1 receptor agonists in Phase III clinical trials.

It is approved for use in Belgium for patients with type 2 diabetes who have not achieved adequate control with other antidiabetic therapies, particularly in those with a body mass index of 30 kg/m² or higher.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Semaglutide, once weekly GLP-1 receptor agonist (Ozempic®)]. Scheen, AJ.[2019]

Semaglutide, administered once weekly, demonstrated superior reductions in HbA1c levels compared to liraglutide, with significant differences noted at various dosages, indicating better long-term glycemic control.

In terms of weight reduction, semaglutide also showed greater efficacy than liraglutide at certain doses, suggesting it may be a more effective option for managing both blood sugar and weight in patients with diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly Semaglutide vs. Liraglutide Efficacy Profile: A Network Meta-Analysis. Alsugair, HA., Alshugair, IF., Alharbi, TJ., et al.[2021]

In a meta-analysis of 23 randomized trials involving 22,096 patients with type 2 diabetes, semaglutide was not found to significantly increase the overall risk of diabetic retinopathy (DR) compared to control groups.

However, the analysis indicated that semaglutide was associated with a higher risk of DR in specific subgroups, particularly in patients aged 60 years or older and those with a diabetes duration of 10 years or more, suggesting that caution is warranted in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide and Diabetic Retinopathy Risk in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials. Wang, F., Mao, Y., Wang, H., et al.[2022]

Semaglutide (Ozempic®) is a new subcutaneous treatment for type 2 diabetes that effectively lowers blood glucose levels by stimulating insulin release and also helps reduce body weight.

The once-weekly injection has been approved in the US, Puerto Rico, and Canada, and is also under review in other countries, with ongoing clinical development for additional conditions like obesity and liver diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide: First Global Approval. Dhillon, S.[2019]

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]

References

1. Japan pubmed.ncbi.nlm.nih.gov

[New drug for type 2 diabetes: introduction of oral Semaglutide (Rybelsus® tablets), an oral GLP-1 receptor agonist]. [2022]

2. Belgium pubmed.ncbi.nlm.nih.gov

[Semaglutide, once weekly GLP-1 receptor agonist (Ozempic®)]. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Weekly Semaglutide vs. Liraglutide Efficacy Profile: A Network Meta-Analysis. [2021]

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

Semaglutide and Diabetic Retinopathy Risk in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials. [2022]

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

Semaglutide: First Global Approval. [2019]

6. 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]

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]