Tirzepatide

SURPASS-2 was a 40-week open-label, randomized, head-to-head trial of tirzepatide (5 mg, 10 mg, or 15 mg weekly) versus semaglutide 1 mg weekly in 1,879 patients with type 2 diabetes on metformin. Mean HbA1c reductions were -2.01% (5 mg), -2.24% (10 mg), -2.30% (15 mg) for tirzepatide versus -1.86% for semaglutide. Body weight reductions were -7.6, -9.3, -11.2 kg for the tirzepatide arms versus -5.7 kg for semaglutide. All tirzepatide doses met non-inferiority and superiority criteria for HbA1c reduction.

Researchers directly compared tirzepatide to semaglutide in nearly 1,900 people with type 2 diabetes over 40 weeks. All three tested doses of tirzepatide led to bigger reductions in long-term blood sugar (HbA1c) and bigger weight loss than semaglutide. The highest tirzepatide dose led to about 25 pounds of weight loss on average, compared to about 13 pounds with semaglutide.

SURMOUNT-1 randomized 2,539 adults with BMI ≥30 (or ≥27 with weight-related comorbidities and without diabetes) to tirzepatide 5 mg, 10 mg, or 15 mg weekly versus placebo for 72 weeks. Mean body-weight reductions were -15.0%, -19.5%, and -20.9% across the three tirzepatide doses versus -3.1% for placebo. The proportion achieving ≥20% weight reduction was 50% in the 15 mg group versus 3% in placebo. The adverse-event profile was consistent with the incretin class — predominantly gastrointestinal and typically transient.

In a 72-week study of about 2,500 adults with overweight or obesity (no diabetes), people receiving weekly tirzepatide injections lost between 15% and 21% of their starting body weight, depending on dose. Placebo group lost about 3%. At the highest dose, half of participants lost 20% or more of their body weight. Side effects were mostly stomach-related and improved over time.