Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 34170647 · doi:10.1056/NEJMoa2107519
What was done
In an open-label, 40-week, phase 3 randomized trial (SURPASS-2), 1879 patients with type 2 diabetes (mean baseline HbA1c 8.28%, mean age 56.6 years, mean weight 93.7 kg) were randomly assigned in a 1:1:1:1 ratio to receive once-weekly subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or once-weekly subcutaneous semaglutide (1 mg). The primary end point was the change in HbA1c level from baseline to 40 weeks.
What was found
Estimated mean HbA1c reductions from baseline were -2.01 percentage points (5 mg), -2.24 percentage points (10 mg), and -2.30 percentage points (15 mg) with tirzepatide compared to -1.86 percentage points with semaglutide. The estimated differences between tirzepatide (5 mg, 10 mg, and 15 mg) and semaglutide were -0.15 percentage points (95% 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, demonstrating noninferiority and superiority. Body weight reductions were greater with tirzepatide (least-squares mean differences of -1.9 kg, -3.6 kg, and -5.5 kg for 5, 10, and 15 mg vs semaglutide, respectively; P<0.001 for all). Gastrointestinal events were the most common adverse effects (nausea: 17–22% vs 18%; diarrhea: 13–16% vs 12%; vomiting: 6–10% vs 8% for tirzepatide vs semaglutide). Serious adverse events occurred in 5% to 7% of patients taking tirzepatide versus 3% taking semaglutide; hypoglycemia (<54 mg/dL) occurred in 0.2% to 1.7% versus 0.4%.
Why it matters
This trial shows that the dual GIP/GLP-1 receptor agonist tirzepatide leads to greater improvements in glycemic control and body weight reduction than the selective GLP-1 receptor agonist semaglutide 1 mg.
Limits
The study used an open-label design, which could affect subjective adverse event reporting. The active comparator was limited to 1 mg of semaglutide, and the 40-week duration does not provide long-term cardiovascular or microvascular outcomes.
Cited by
- contradicts Tirzepatide produces more weight loss per milligram than any other commercially available GLP-1 drug.