What do we already know about this topic?

• Tirzepatide is a multi-functional peptide engineered from the native glucose-dependent insulinotropic polypeptide (GIP).
• It is modified to bind to both GIP and glucagon-like peptide-1 (GLP-1) receptors.
• The mechanism of action is likely due to synergistic and complementary effects of the dual agonism.
• In Phase 2 and 3 clinical trials, significant reductions in HbA1c were seen across the spectrum of type 2 diabetes (T2D).

How was this study conducted?

• SURMOUNT-1 was a randomized trial of tirzepatide in obesity management.
• 2,539 people with body mass index (BMI) ≥30 (or ≥27 with a weight-related comorbidity) were allocated to placebo, or 5, 10, or 15 mg tirzepatide once-weekly for 72 weeks.
• There was also a 2-year additional treatment period for those with prediabetes.
• Results were stratified by two estimands:
  • Treatment regimen estimand: the treatment difference regardless of adherence to randomized treatment
  • Efficacy estimand: if all patients remained on treatment for 72 weeks.
• The primary endpoint was weight reduction over 72 weeks.