Eli Lilly's Orforglipron Successfully Completes Phase 3 Trial for Type 2 Diabetes Treatment

Eli Lilly and Company announced results from ACHIEVE-1, a Phase 3 trial evaluating the safety and efficacy of orforglipron in adults with type 2 diabetes. All three doses of orforglipron (3 mg, 12 mg, and 36 mg) achieved the primary endpoint of superior A1C reduction at 40 weeks. Orforglipron is the first oral small molecule GLP-1 receptor agonist to complete a Phase 3 trial. Lilly is running Phase 3 studies for type 2 diabetes and weight management, as well as for obstructive sleep apnea and hypertension in adults with obesity.

Eli Lilly and Company (NYSE: LLY) has announced the results of ACHIEVE-1, a Phase 3 trial evaluating the safety and efficacy of orforglipron in adults with type 2 diabetes. The trial, which compared orforglipron to placebo, demonstrated significant improvements in glycemic control and weight management. Orforglipron, an oral small molecule GLP-1 receptor agonist, is the first of its kind to successfully complete a Phase 3 trial.

The primary endpoint of the trial, which involved 559 participants across five countries, was to assess the superiority of orforglipron in reducing hemoglobin A1c (HbA1c) levels compared to placebo. All three doses of orforglipron (3 mg, 12 mg, and 36 mg) achieved this primary endpoint, with average reductions in HbA1c ranging from 1.3% to 1.6% from a baseline of 8.0% [1].

In addition to the primary endpoint, the trial also evaluated secondary endpoints, including weight reduction and fasting serum glucose levels. Participants taking the highest dose of orforglipron lost an average of 16.0 lbs (7.9%) at week 40, while those taking the 12 mg dose lost an average of 5.5 lbs (2.5%). The reductions in fasting serum glucose levels ranged from 30.6 mg/dL to 37.4 mg/dL across the different doses [1].

The safety profile of orforglipron was consistent with the established GLP-1 class, with gastrointestinal-related adverse events being the most common. These included diarrhea, nausea, dyspepsia, constipation, and vomiting, which were generally mild to moderate in severity and occurred primarily during dose escalation [1].

Lilly is planning to share topline results from two additional Phase 3 trials, ACHIEVE-2 and ACHIEVE-3, later this year. These trials will evaluate orforglipron compared to dapagliflozin and oral semaglutide, respectively, in adults with type 2 diabetes inadequately controlled with metformin. Additionally, Lilly is running Phase 3 studies for weight management, as well as for obstructive sleep apnea and hypertension in adults with obesity.

The results of ACHIEVE-1 position orforglipron as a potential treatment option for type 2 diabetes, with meaningful improvements in glycemic control and weight reduction, and a safety profile similar to injectable GLP-1 therapies. Lilly remains on track to submit orforglipron for weight management to global regulatory agencies by the end of this year and for the treatment of type 2 diabetes in 2026 [1].

References:
[1] https://investor.lilly.com/news-releases/news-release-details/lillys-oral-glp-1-orforglipron-showed-compelling-efficacy-and