“Tirzepatide versus Semaglutide Once Weekly in Patients With Type 2 Diabetes [SURPASS-2]”, 2021-08-05 (; backlinks):
Background: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and gglucagon-like peptide-1(GLP-1) receptor agonist that is under development for the treatment of type 2 diabetes. The efficacy and safety of once-weekly tirzepatide as compared with semaglutide, a selective GLP-1 receptor agonist, are unknown.
Method: In an open-label, 40-week, phase 3 trial [SURPASS-2; followup to SURPASS-1; next], we randomly assigned 1,879 patients, in a 1:1:1:1 ratio, to receive tirzepatide at a dose of 5 mg, 10 mg, or 15 mg or semaglutide at a dose of 1 mg. At baseline, the mean glycated hemoglobin level was 8.28%, the mean age 56.6 years, and the mean weight 93.7 kg. The primary end point was the change in the glycated hemoglobin level from baseline to 40 weeks.
Results: The estimated mean change from baseline in the glycated hemoglobin level was −2.01 percentage points, −2.24 percentage points, and −2.30 percentage points with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and −1.86 percentage points with semaglutide; the estimated differences between the 5-mg, 10-mg, and 15-mg tirzepatide groups and the semaglutide group were −0.15 percentage points (95% confidence interval [CI], −0.28 to −0.03; p = 0.02), −0.39 percentage points (95% CI, −0.51 to −0.26; p < 0.001), and −0.45 percentage points (95% CI, −0.57 to −0.32; p < 0.001), respectively. Tirzepatide at all doses was non-inferior and superior to semaglutide.
Reductions in body weight were greater with tirzepatide than with semaglutide (least-squares mean estimated treatment difference, −1.9 kg, −3.6 kg, and −5.5 kg, respectively; p < 0.001 for all comparisons).
The most common adverse events were gastrointestinal and were primarily mild to moderate in severity in the tirzepatide and semaglutide groups (nausea, 17 to 22% and 18%; diarrhea, 13 to 16% and 12%; and vomiting, 6 to 10% and 8%, respectively). Of the patients who received tirzepatide, hypoglycemia (blood glucose level, <54 mg per deciliter) was reported in 0.6% (5-mg group), 0.2% (10-mg group), and 1.7% (15-mg group); hypoglycemia was reported in 0.4% of those who received semaglutide. Serious adverse events were reported in 5 to 7% of the patients who received tirzepatide and in 3% of those who received semaglutide.
Conclusion: In patients with type 2 diabetes, tirzepatide was non-inferior and superior to semaglutide with respect to the mean change in the glycated hemoglobin level from baseline to 40 weeks.
Funding: Funded by Eli Lilly and Company; SURPASS-2 ClinicalTrials.gov number, NCT03987919.
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