Eli Lilly and Company announced Tirzepatide led to superior A1C and body weight reductions from baseline compared to injectable semaglutide 1 mg in 40-week results from company's SURPASS-2 clinical trial, which were simultaneously published in The New England Journal of Medicine (NEJM) and presented in a late breaking poster presentation during the American Diabetes Association's® (ADA) 81st Scientific Sessions®. These results, which will also be featured during an ADA-sponsored symposium on, June 29, showed that all three tirzepatide doses achieved greater A1C and weight reductions compared to semaglutide. Additionally, a prespecified exploratory composite endpoint comprised of participants who achieved an A1C level less than or equal to 6.5% and weight loss of 10% or greater, while not experiencing hypoglycemia less than 54 mg/dL or severe hypoglycemia, was evaluated. Across the three doses of tirzepatide, 32% (5 mg), 51% (10 mg) and 60% (15 mg) of participants achieved this composite endpoint compared to 22% of participants taking semaglutide 1 mg.1,2 The overall safety profile of tirzepatide was similar to the well-established glucagon-like peptide-1 (GLP-1) receptor agonist class. Across all treatment arms, the most commonly reported adverse events were gastrointestinal-related. SURPASS-2 was a 40-week, randomized, open-label trial comparing the efficacy and safety of tirzepatide to semaglutide as an add-on to metformin in adults with type 2 diabetes. The study randomized 1,879 participants, who had a mean duration of diabetes of 8.6 years, a baseline A1C of 8.28 percent and a baseline weight of 93.7 kg. For both estimandsi, all three doses of tirzepatide demonstrated superior A1C and body weight reductions compared to semaglutide 1 mg. Specifically, the efficacy estimandii results showed: A1C reduction: -2.09% (5 mg), -2.37% (10 mg), -2.46% (15 mg), -1.86% (semaglutide); Weight reduction: -7.8 kg (-8.5%, 5 mg), -10.3 kg (-11.0%, 10 mg), -12.4 kg (-13.1%, 15 mg), -6.2 kg (-6.7%, semaglutide); Percent of participants achieving A1C <7%: 85% (5 mg), 89% (10 mg), 92% (15 mg), 81% (semaglutide); Percent of participants achieving A1C <5.7%: 29% (5 mg, not controlled for type 1 error), 45% (10 mg), 51% (15 mg), 20% (semaglutide). Hypoglycemia less than 54 mg/dL was reported in 0.6% (5 mg), 0.2% (10 mg) and 1.7% (15 mg) of participants in the tirzepatide arms and in 0.4% of participants in the semaglutide arm. In an additional exploratory endpoint, all three doses of tirzepatide led to favorable changes from baseline in fasting lipids. Specifically, at the highest dose of tirzepatide (15 mg): triglycerides were reduced by 24.8%, very low-density lipoprotein (VLDL) cholesterol was reduced by 23.7%, and high-density lipoprotein (HDL) cholesterol was increased by 7.1%. SURPASS-2 is the second of five global registration studies for tirzepatide in type 2 diabetes, all of which have been completed. Lilly intends to submit the full registration package to regulatory authorities by the end of 2021.