Lilly announces results of ACHIEVE-3 trial for type 2 diabetes

Eli Lilly reports that the ACHIEVE-3 trial shows orforglipron significantly lowers A1C and promotes weight loss in adults with type 2 diabetes compared to oral semaglutide, highlighting its potential as an effective new treatment option worldwide.

Eli Lilly and Company has published comprehensive results from the ACHIEVE-3 Phase III clinical trial. This trial aimed to assess the effectiveness and safety of orforglipron in comparison to oral semaglutide in adults with type 2 diabetes (T2D), particularly those whose diabetes was insufficiently controlled with metformin alone. The results, featured in The Lancet, show that orforglipron demonstrated superior performance in reducing A1C levels and achieving weight loss compared to oral semaglutide.

Study Design and Patient Enrollment

The ACHIEVE-3 trial was a randomized, open-label study spanning 52 weeks. It involved 1,698 participants from various countries, including China, Argentina, Mexico, Japan, the United States, and Puerto Rico. The participants were assigned to one of four treatment groups:

• Orforglipron 12mg
• Orforglipron 36mg
• Oral semaglutide 7mg
• Oral semaglutide 14mg

The primary objective of the trial was to determine if orforglipron was at least as effective as oral semaglutide in lowering A1C levels after 52 weeks of treatment.

Dosing Protocol

For those on orforglipron, treatment began with a 1mg daily dose, which was gradually increased every four weeks until participants reached a maintenance dose of either 12mg or 36mg. Participants receiving oral semaglutide started with a 3mg daily dose, which was titrated up to either 7mg or 14mg. Dose adjustments were allowed for tolerability, with minimum doses set at 3mg for orforglipron and 7mg for oral semaglutide.

Global ACHIEVE Program

The ACHIEVE Phase III clinical program for orforglipron includes more than 6,000 adults with T2D across five registration trials. Initiated in 2023, additional data from three remaining trials will be released later this year, further examining the drug's efficacy and safety profile.

Key Findings

The ACHIEVE-3 trial highlighted several key findings that favor orforglipron over oral semaglutide:

• Orforglipron led to greater reductions in A1C levels.
• Significant weight loss was observed in the orforglipron groups.
• Improvements in cardiovascular risk factors, including systolic blood pressure, triglycerides, and cholesterol subtypes.

Kenneth Custer, Lilly’s Executive Vice President and President of Cardiometabolic Health, emphasized that the results of the trial suggest that orforglipron may offer distinct advantages over oral semaglutide for managing type 2 diabetes. The combination of greater A1C reduction, more pronounced weight loss, and the ability to take the medication without food or water restrictions could have a significant impact on day-to-day disease management for patients.

Safety and Tolerability

The safety profile of orforglipron in the ACHIEVE-3 trial was consistent with previous studies. The most common side effects reported were nausea, diarrhea, vomiting, dyspepsia, and reduced appetite. The rate of discontinuation due to adverse events ranged from 8.7% to 9.7% for orforglipron, while for oral semaglutide, it was between 4.5% and 4.9%.

Regulatory Status

Lilly has submitted orforglipron for regulatory review in over 40 countries. A submission for approval in the United States is expected later this year. The company is actively seeking approval to expand patient access to this new treatment option for type 2 diabetes.

Additional Developments

In addition to the progress with orforglipron, Lilly has made significant strides with other treatments in its portfolio. For example, Omvoh (mirikizumab), a treatment for Crohn’s disease, has shown promising results in maintaining corticosteroid-free status and supporting long-term clinical remission in patients. This reflects Lilly's ongoing commitment to advancing its therapeutic offerings in various areas of medicine.

Conclusion

The results of the ACHIEVE-3 Phase III trial provide strong evidence that orforglipron may offer enhanced efficacy compared to oral semaglutide for managing type 2 diabetes. With further data expected later this year from the ongoing global ACHIEVE program, Lilly continues to make significant progress in providing improved treatment options for adults with T2D who struggle with inadequate control from standard therapies.

Sources:

• Lilly’s oral GLP‑1, orforglipron, delivered superior blood sugar control and weight loss compared to oral semaglutide in head‑to‑head type 2 diabetes trial published in The Lancet
• Lilly reports ACHIEVE‑3 trial outcomes for type 2 diabetes
• Lilly announces superior results in type 2 diabetes trial of oral orforglipron versus oral semaglutide
• Lilly reports ACHIEVE-3 trial outcomes for type 2 diabetes