Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
tirzepatide at a dose of 5 mg | decrease | glycated hemoglobin level | patients with type 2 diabetes | -2.01 percentage points | estimated mean change from baseline | #1 |
tirzepatide at a dose of 10 mg | decrease | glycated hemoglobin level | patients with type 2 diabetes | -2.24 percentage points | estimated mean change from baseline | #2 |
tirzepatide at a dose of 15 mg | decrease | glycated hemoglobin level | patients with type 2 diabetes | -2.30 percentage points | estimated mean change from baseline | #3 |
semaglutide at a dose of 1 mg | decrease | glycated hemoglobin level | patients with type 2 diabetes | -1.86 percentage points | estimated mean change from baseline | #4 |
tirzepatide at a dose of 5 mg | decrease | glycated hemoglobin level | patients with type 2 diabetes | -0.15 percentage points | estimated difference | #5 |
tirzepatide at a dose of 10 mg | decrease | glycated hemoglobin level | patients with type 2 diabetes | -0.39 percentage points | estimated difference | #6 |
tirzepatide at a dose of 15 mg | decrease | glycated hemoglobin level | patients with type 2 diabetes | -0.45 percentage points | estimated difference | #7 |
tirzepatide at all doses | decrease | glycated hemoglobin level | patients with type 2 diabetes | - | was noninferior and superior | #8 |
tirzepatide | decrease | body weight | patients with type 2 diabetes | -1.9 kg, -3.6 kg, and -5.5 kg | reductions in body weight were greater | #9 |
tirzepatide | increase | nausea | patients with type 2 diabetes | 17 to 22% | most common adverse events were gastrointestinal | #10 |
semaglutide | increase | nausea | patients with type 2 diabetes | 18% | most common adverse events were gastrointestinal | #11 |
tirzepatide | increase | diarrhea | patients with type 2 diabetes | 13 to 16% | most common adverse events were gastrointestinal | #12 |
semaglutide | increase | diarrhea | patients with type 2 diabetes | 12% | most common adverse events were gastrointestinal | #13 |
tirzepatide | increase | vomiting | patients with type 2 diabetes | 6 to 10% | most common adverse events were gastrointestinal | #14 |
semaglutide | increase | vomiting | patients with type 2 diabetes | 8% | most common adverse events were gastrointestinal | #15 |
tirzepatide at a dose of 5 mg | increase | hypoglycemia | patients with type 2 diabetes | 0.6% | hypoglycemia was reported | #16 |
tirzepatide at a dose of 10 mg | increase | hypoglycemia | patients with type 2 diabetes | 0.2% | hypoglycemia was reported | #17 |
tirzepatide at a dose of 15 mg | increase | hypoglycemia | patients with type 2 diabetes | 1.7% | hypoglycemia was reported | #18 |
semaglutide at a dose of 1 mg | increase | hypoglycemia | patients with type 2 diabetes | 0.4% | hypoglycemia was reported | #19 |
tirzepatide | increase | serious adverse events | patients with type 2 diabetes | 5 to 7% | serious adverse events were reported | #20 |
semaglutide | increase | serious adverse events | patients with type 2 diabetes | 3% | serious adverse events were reported | #21 |
BACKGROUND: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-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. METHODS: In an open-label, 40-week, phase 3 trial, we randomly assigned 1879 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 noninferior 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. CONCLUSIONS: In patients with type 2 diabetes, tirzepatide was noninferior and superior to semaglutide with respect to the mean change in the glycated hemoglobin level from baseline to 40 weeks. (Funded by Eli Lilly; SURPASS-2 ClinicalTrials.gov number, NCT03987919.).