Key inclusion criteria for this study were

• T2D
• glycated hemoglobin (HbA1c) ≥7.0% and ≤9.5%
• body mass index (BMI) ≥23 kg/m² with stable weight, and
• naïve to T2D injectable therapy.2
  

Key exclusion criteria for this study were

• type 1 diabetes (T1D)
• history of pancreatitis
• estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m²
  
• use of any oral antihyperglycemic medication (OAM) in the 3 months prior to screening.2
  

The SURPASS-1 study randomized 478 study participants across the United States, Mexico, India, and Japan in 1:1:1:1 ratio to receive tirzepatide 5, 10, or 15 mg, or placebo.2

The primary objective of this study was to demonstrate that tirzepatide 5, 10, and 15 mg once weekly are superior compared with placebo for mean change from baseline in HbA1c to 40 weeks.2

The 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-1 Study Design).2

Baseline demographics and clinical characteristics of randomized patients are presented in SURPASS-1: Baseline Demographics and Clinical Characteristics.2

Treatment discontinuation in SURPASS-1 is summarized in Summary of Treatment Discontinuation in SURPASS-1  . Reasons leading to treatment discontinuation were adverse event (AE), death, did not meet randomization criteria, loss to follow-up, physician decision, protocol deviation, withdrawal by participant, or other.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

In the SURPASS-1 study, tirzepatide 5, 10, and 15 mg were superior compared with placebo at 40 weeks for

• mean change in HbA1c from baseline
  
• mean change in weight from baseline
• mean change in fasting serum glucose (FSG) from baseline
• proportion of participants achieving HbA1c <7.0%, and
• proportion of participants achieving HbA1c <5.7% (SURPASS-1: Primary and Other Secondary Endpoints at Week 40).2

The most frequently reported AEs were gastrointestinal in nature. Most reports of nausea, vomiting, and diarrhea were mild to moderate in severity and transient and usually occurred during the dose escalation period. Overview of AEs and treatment-emergent adverse events (TEAEs) with ≥5% frequency are provided in Overview of Adverse Events Through 40 Weeks in SURPASS-1  and Treatment-Emergent Adverse Events With ≥5% Frequency Through 40 Weeks in SURPASS-1.1,2

No events of severe or clinically significant hypoglycemia (blood glucose <54 mg/dL) were observed in the tirzepatide treatment arms (Hypoglycemia Frequency Through 40 Weeks in SURPASS-1).2