Lilly's oral GLP-1, orforglipron, is successful in third Phase 3 trial, triggering global regulatory submissions this year for the treatment of obesity

Core Insights - Eli Lilly announced positive topline results from the Phase 3 ATTAIN-2 trial for orforglipron, an investigational oral GLP-1 receptor agonist, showing significant weight loss and A1C reductions in adults with obesity or overweight and type 2 diabetes [1][2][4] Efficacy Results - Orforglipron 36 mg led to an average weight loss of 22.9 lbs (10.5%) and a reduction in A1C by 1.8% after 72 weeks, compared to 5.1 lbs (2.2%) weight loss and 0.1% A1C reduction in the placebo group [1][2] - In the trial, 75% of participants on the highest dose achieved an A1C ≤6.5%, meeting the American Diabetes Association's definition of diabetes [2][4] - The trial demonstrated that orforglipron met all primary and key secondary endpoints, including significant improvements in cardiometabolic risk factors [1][4] Safety Profile - The safety profile of orforglipron was consistent with established GLP-1 receptor agonists, with the most common adverse events being gastrointestinal-related, such as nausea (20.1% to 36.4%), vomiting (12.8% to 23.1%), and diarrhea (21.3% to 27.4%) across different doses [4][8] - Treatment discontinuation rates due to adverse events were 6.1% for 6 mg, 10.6% for 12 mg, and 10.6% for 36 mg, compared to 4.6% for placebo, indicating a balanced overall treatment discontinuation rate [4][8] Regulatory Pathway - With the completion of the ATTAIN-2 trial, Eli Lilly is prepared to initiate global regulatory submissions for orforglipron, aiming to provide a convenient, once-daily oral treatment option for obesity and type 2 diabetes [1][4][6] Clinical Trial Details - The ATTAIN-2 trial was a 72-week, randomized, double-blind, placebo-controlled study involving over 1,600 participants across multiple countries, focusing on the efficacy and safety of orforglipron [7][8]