SURPASS-2: tirzepatide vs. semaglutide
Results from the open-label, randomised SURPASS-2 trial, assessing the novel dual GIP (glucose-dependent insulinotropic polypeptide)/GLP-1 (glucagon-like peptide 1) receptor agonist tirzepatide vs. human GLP-1 receptor agonist semaglutide in 1,878 type 2 diabetes patients inadequately controlled with metformin, conferred statistically significant HbA1c and body weight reductions from baseline compared to semaglutide in all three treatment arms (tirzepatide 5 mg, 10 mg, and 15 mg).
At 40 weeks, all once-weekly tirzepatide doses were found to be noninferior and superior to semaglutide 1 mg once weekly with respect to the mean change in HbA1c level from baseline, the primary outcome, delivering HbA1c reductions of -2.01% (5 mg), -2.24% (10 mg), and -2.30% (15 mg) vs. -1.86% with semaglutide.
Mean reductions in body weight at 40 weeks were greater with tirzepatide compared with semaglutide and were dose-dependent, with 5 mg, 10 mg and 15 mg tirzepatide doses resulting in mean body weight reductions of 7.6 kg, 9.3 kg and 11.2 kg, respectively, compared with 5.7 kg with semaglutide.
Pre-specified exploratory analyses assessed the proportion of patients achieving an HbA1c ≤ 6.5% and weight loss of 10% or greater, without experiencing clinically significant hypoglycaemia (blood glucose < 54 mg/dL) or severe hypoglycaemia to be 32%-60% in the tirzepatide arms vs 22% on semaglutide 1 mg.
Consistent with adverse events expected with the GLP-1 receptor agonist class, the most common adverse events reported in the trial were mild to moderate gastrointestinal events including nausea, 17 to 22% in tirzepatide groups and 18% in semaglutide group; diarrhoea 13 to 16% and 12%; and vomiting, 6 to 10% and 8% respectively.
A total of 13 deaths (0.7%) occurred in the total population during the trial (4 patients in each of the three tirzepatide groups and 1 patient in the semaglutide group). 5 deaths were related to COVID-19, and a 6th suspected.