Tirzepatide achieved superior A1C and body weight reductions across all three doses compared to injectable semaglutide in adults with type 2 diabetes
INDIANAPOLIS,?March 4, 2021?/PRNewswire/ -- 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?(NYSE: LLY) 40-week SURPASS-2 clinical trial. In topline results from the largest SURPASS trial to date, using the efficacy estimandi, 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 Fr?as, 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 estimandsii, 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. Specifically, results showed:
In the treatment-regimen estimandiii, 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:
Efficacy Estimand Results | ||||
Tirzepatide 5 mg | Tirzepatide 10 mg | Tirzepatide 15 mg | Semaglutide 1 mg | |
A1C reduction from baseline of 8.28% | -2.09%* | -2.37%* | -2.46%* | -1.86% |
Weight reduction from baseline of 93.7 kg | -7.8 kg* (-8.5%) | -10.3 kg* (-11.0%) | -12.4 kg* (-13.1%) | -6.2 kg (-6.7%) |
Percent of participants achieving A1C <7% | 85.5%* | 88.9%* | 92.2%* | 81.1% |
Percent of participants achieving A1C <5.7% | 29.3%? | 44.7%* | 50.9%* | 19.7% |
*Denotes statistical significance compared to semaglutide ?Not controlled for type I error |
- A1C reduction: -2.01% (5 mg), -2.24% (10 mg), -2.30% (15 mg), -1.86% (semaglutide)
- Weight reduction:?-7.6 kg (5 mg), -9.3 kg (10 mg), -11.2 kg (15 mg), -5.7 kg (semaglutide)
- Percent of participants achieving A1C <7%: 82.0% (5 mg), 85.6% (10 mg), 86.2% (15 mg), 79.0% (semaglutide)
- Percent of participants achieving A1C <5.7%: 27.1% (5 mg), 39.8% (10 mg), 45.7% (15 mg), 18.9% (semaglutide)