Tirzepatide achieved superior A1C and body weight reductions across all three doses compared to injectable semaglutide in adults with type 2 diabetes.- Eli Lilly

The SURPASS phase III global clinical development program for tirzepatide has enrolled more than 13,000 people with type 2 diabetes across 10 clinical trials, five of which are global registration studies. The program began in late 2018 with full results from the registration studies anticipated in 2021. Tirzepatide led to superior A1C and body weight reductions from baseline across all three doses compared to injectable semaglutide 1 mg in adults with type 2 diabetes in Eli Lilly and Company's 40-week SURPASS-2 clinical trial . In topline results from the largest SURPASS trial to date, using the efficacy estimand, the highest dose of tirzepatide (15 mg) reduced A1C by 2.46 percent and body weight by 12.4 kg (27.3 lb., 13.1 percent). The lowest dose of tirzepatide (5 mg) reduced A1C by 2.09 percent and body weight by 7.8 kg (17.2 lb., 8.5 percent) compared to semaglutide at 1.86 percent and 6.2 kg (13.7 lb., 6.7 percent). Additionally, 51 percent of those taking tirzepatide 15 mg achieved an A1C of less than 5.7 percent – the level seen in people without diabetes – compared to 20 percent of those taking semaglutide. The overall safety profile of tirzepatide was similar to previously reported SURPASS trials and 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. Tirzepatide is a novel investigational once-weekly dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist that integrates the actions of both incretins into a single molecule, representing a new class of medicines being studied for the treatment of type 2 diabetes. Semaglutide is a GLP-1 receptor agonist for the treatment of type 2 diabetes. "Head-to-head studies are the gold standard for clinicians assessing the efficacy of investigational treatments, and these results show that all three doses of tirzepatide delivered superior A1C and weight reductions compared to the highest approved dose of semaglutide to treat type 2 diabetes," said Juan Pablo Frías, M.D., Medical Director, National Research Institute and Principal Investigator of SURPASS-2. "Newer treatment options may help people with type 2 diabetes achieve their A1C and weight loss goals. In SURPASS-2, tirzepatide delivered clinically meaningful efficacy, beyond what has been seen with an existing medicine in the established GLP-1 receptor agonist class." 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. Across both estimands, all three doses of tirzepatide (5 mg, 10 mg and 15 mg) delivered superior A1C and body weight reductions compared to semaglutide. Of the participants receiving tirzepatide 15 mg, 92 percent achieved an A1C of less than 7 percent, the American Diabetes Association's recommended target for people with diabetes, compared to 81 percent of those taking semaglutide. . In the treatment-regimen estimand, all three doses of tirzepatide delivered superior A1C and body weight reductions compared to semaglutide . Greater percentages of participants achieved an A1C of less than 7 percent across all three doses compared to semaglutide, with statistical significance met for 10 mg and 15 mg but not for 5 mg. Specifically, results showed: i. A1C reduction: -2.01% (5 mg), -2.24% (10 mg), -2.30% (15 mg), -1.86% (semaglutide).ii. Weight reduction: -7.6 kg (5 mg), -9.3 kg (10 mg), -11.2 kg (15 mg), -5.7 kg (semaglutide). iii. Percent of participants achieving A1C <7%: 82.0% (5 mg), 85.6% (10 mg), 86.2% (15 mg), 79.0% (semaglutide). iv. percent of participants achieving a1c><5.7%: 27.1% (5 mg), 39.8% (10 mg), 45.7% (15 mg), 18.9% (semaglutide. v.hypoglycemia less than 54 mg dl was reported in 0.6 percent (5 mg), 0.2 percent (10 mg) and 1.7 percent (15 mg) of participants in the tirzepatide arms and in 0.4 percent of participants in the semaglutide arm. the most commonly reported adverse events across all treatment arms were gastrointestinal-related , including nausea (17.4 percent [5 mg], 19.2 percent [10 mg], 22.1 percent [15 mg], 17.9 percent [semaglutide]), diarrhea (13.2 percent [5 mg], 16.4 percent [10 mg], 13.8 percent [15 mg], 11.5 percent [semaglutide]) and vomiting (5.7 percent [5 mg], 8.5 percent [10 mg], 9.8 percent [15 mg], 8.3 percent [semaglutide]). treatment discontinuation rates due to adverse events were 5.1 percent (5 mg), 7.7 percent (10 mg), 7.9 percent (15 mg) and 3.8 percent (semaglutide). the complete surpass-2 study data have not yet been evaluated but will be presented at the american diabetes association's 81st scientific sessions and published in a peer-reviewed publication in 2021.. efficacy estimand represents efficacy prior to discontinuation of study drug or initiating rescue therapy for persistent severe hyperglycemia.treatment differences for two estimands – efficacy and treatment-regimen – were evaluated for three tirzepatide doses (5 mg, 10 mg and 15 mg) compared to semaglutide 1 mg.>