Lilly’s Orforglipron Cuts HbA1c 2.2% and 9.2% Weight Loss Versus Semaglutide
Eli Lilly’s oral GLP-1 candidate orforglipron 36 mg lowered HbA1c by 2.2% and achieved 9.2% weight loss (19.7 lbs) after 52 weeks, outpacing semaglutide’s 1.4% A1c reduction and 5.3% weight loss. Orforglipron submissions are in over 40 countries with potential U.S. obesity approval forecast for Q2 2026.
1. Trial Design and Efficacy Results
ACHIEVE-3 enrolled 1,698 adults with type 2 diabetes on metformin, randomizing them to orforglipron (12 mg, 36 mg) or oral semaglutide (7 mg, 14 mg) for 52 weeks. Orforglipron 36 mg reduced A1C by 2.2% vs 1.4% for semaglutide 14 mg and delivered 9.2% weight loss (19.7 lbs) vs 5.3% (11.0 lbs).
2. Regulatory Submissions and Outlook
Lilly has submitted orforglipron to regulators in more than 40 countries and expects a U.S. FDA decision on an obesity indication in Q2 2026, with a type 2 diabetes filing planned later in the year.
3. Safety and Tolerability
Discontinuation due to adverse events occurred in 9.7% of patients on orforglipron 36 mg versus 4.9% on semaglutide 14 mg. The most common side effects were nausea, diarrhea, vomiting, dyspepsia and decreased appetite, consistent with previous trials.