Key inclusion criteria for this study were

• T2D
• glycated hemoglobin (HbA1c) ≥7.0% to ≤10.5% at screening
• body mass index (BMI) ≥25 kg/m² with stable weight, and
• stable dose of metformin ≥1500 mg/day.2
  

Key exclusion criteria for this study were

• type 1 diabetes (T1D) 
• history of pancreatitis
  
• estimated glomerular filtration rate (eGFR) <45 mL/min/1.73m²
  
• use of any antihyperglycemic treatment other than metformin in the 3 months prior to screening, and
• history of proliferative diabetic retinopathy or maculopathy (or nonproliferative diabetic retinopathy requiring acute treatment).2 

The SURPASS-2 study is an open-label, 40-week, active-controlled, phase 3 trial that randomized 1879 study participants across the United States, Argentina, Australia, Brazil, Canada, Israel, Mexico, and the United Kingdom in 1:1:1:1 ratio to receive either tirzepatide 5, 10, or 15 mg, or semaglutide 1 mg injection.2

The primary objective of the study was to demonstrate that tirzepatide 10 and/or 15 mg once weekly are noninferior to semaglutide 1 mg once weekly for mean change from baseline in HbA1c at 40 weeks.2

The SURPASS-2 study design included a 40-week study period. The starting dose of tirzepatide was 2.5 mg once weekly for 4 weeks, escalated in 2.5 mg increments every 4 weeks until the assigned dose of 5, 10, or 15 mg was achieved, which took up to 20 weeks (SURPASS-2 Study Design).2

Baseline demographics and clinical characteristics of randomized patients are presented in SURPASS-2: Baseline Demographics and Clinical Characteristics.2

Treatment discontinuation in SURPASS-2 is summarized in Summary of Treatment Discontinuation in SURPASS-2 . In all treatment groups, the most common reasons for study drug discontinuation were adverse events (AEs).2

Two statistical estimands, efficacy or treatment-regimen, were used to evaluate efficacy data from the phase 3 clinical trials of tirzepatide. Efficacy estimand evaluates the treatment effect prior to discontinuation of the study drug without confounding effects of antihyperglycemic rescue therapy. Treatment-regimen estimand evaluates the treatment effect irrespective of adherence to the study drug or initiation of rescue antidiabetic drugs. Differences in reported data may reflect the application of these estimands. This response presents data reflecting the efficacy estimand. For treatment-regimen estimand results, please refer to the manuscript cited and/or the US prescribing information, where applicable.2 

As described in SURPASS-2: Primary and Other Secondary Endpoints at 40 Weeks, in SURPASS-2, tirzepatide 5, 10, and 15 mg were superior compared with semaglutide 1 mg at 40 weeks for

• mean change in HbA1c
• mean change in weight, and
• proportion of participants achieving HbA1c <7%.2

 Tirzepatide 10 and 15 mg were also superior compared with semaglutide 1 mg at 40 weeks for the proportion of participants achieving HbA1c <5.7% .2

The most frequently reported AEs for tirzepatide were gastrointestinal in nature. Most cases of nausea, vomiting, and diarrhea were mild to moderate in severity and transient or usually occurred during the dose escalation period. Overview of AEs and treatment-emergent adverse event (TEAE) with ≥5% frequency are provided in Overview of Adverse Events Through 40 Weeks in SURPASS-2  and Treatment-Emergent Adverse Events Occurring in ≥5% of Patients in SURPASS-2​.2

Hypoglycemia frequency is provided in Hypoglycemia Frequency Through 40 Weeks in SURPASS-2​.​2