On April 17, Eli Lilly released the positive topline results of the Phase 3 clinical study ACHIEVE-1, which evaluated the safety and effectiveness of orforglipron versus placebo in patients with type 2 diabetes who still have poor blood sugar control based on dietary control and exercise. Orforglipron is an oral small molecule glucagon-like peptide-1 (GLP-1) receptor agonist that completes phase 3 trials without restricting diet or water.

“At present, there are seven phase 3 clinical trials that evaluate the safety and effectiveness of orforglipron in diabetes and obese people, ACHIEVE-1 is the first of them. As the latest incretin drug, we are pleased to see that it meets our expectations for its safety, tolerance, glycemic control and weight loss, and we will obtain more data on this study by the end of this year.” Lilly Pharmaceutical Chairman and CEO Dai Wenrui said, “As a once-daily oral drug that is convenient for administration, orforglipron will provide patients with a new treatment option. If the drug is approved, it will be able to be mass-produced and marketed to benefit patients around the world.”

In the first phase 3 clinical trial of the ACHIEVE program, orforglipron reached the primary endpoint, that is, at 40 weeks, the decline in glycosylated hemoglobin (A1C) was significantly better than the placebo group, with A1C falling by an average of 1.3% to 1.6% from 8.0% baseline (using the effectiveness estimate target). At the critical secondary endpoint, more than 65% of patients received the highest dose of orforglipron and A1C value dropped to ≤6.5%, lower than the American Diabetes Association (ADA)-defined diabetes threshold. At another key secondary endpoint, patients receiving orforglipron lost an average of 7.3 kg (7.9%) at the highest dose. Given that the patient did not reach the plateau of weight at the end of the study, it may be a sign that the complete weight loss has not been achieved.

For treatment regimen estimation targets, each dose group of orforglipron showed a statistically significant reduction in A1C. Among the key secondary endpoints of body weight, the 12 mg and 36 mg dose groups showed statistically significant reductions.

A1C decrease: 1.2% in the 3mg group, 1.5% in the 12mg group, 1.5% in the 36mg group, and 0.4% in the placebo group

· Percentage of weight loss: 4.5% reduction in the 3mg group, 5.8% reduction in the 12mg group, 7.6% reduction in the 36mg group, and 1.7% reduction in the placebo group

Weight loss: 4.2kg in the 3mg group, 5.2kg in the 12mg group, 7.2kg in the 36mg group, and 1.5kg in the placebo group

In the ACHIEVE-1 study, the overall safety of orforglipron is consistent with that of the GLP-1 drug. The most common adverse reaction is gastrointestinal reaction, usually mild to moderate. The most common adverse events in patients receiving orforglipron (3 mg, 12 mg, and 36 mg) were: diarrhea (19%, 21%, and 26%) vs placebo group 9%; nausea (13%, 18%, and 16%) vs placebo group 2%; dyspepsia (10%, 20%, and 15%) vs placebo group 7%; constipation (8%, 17%, and 14%) vs placebo group 4%; vomiting (5%, 7%, and 14%) vs placebo group 1%. The overall treatment interruption rates due to adverse events were: 6% in the 3mg group, 4% in the 12mg group, 8% in the 36mg group, and 1% in the placebo group. No liver safety signals were observed.

It is reported that the results of the ACHIEVE-1 study will be published at the 85th ADA Science Conference and published in peer-reviewed journals. It is expected that more results of the Phase 3 clinical trial project of ACHIEVE study will be released by the end of this year, as well as the Phase 3 clinical study of the ATTAIN study by orforglipron for weight management. Eli Lilly is expected to submit an orforglipron listing application for weight management to global regulators by the end of this year, and it is expected to submit its listing application for type 2 diabetes in 2026.

[Editor in charge: Sun Hui]