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 glycated hemoglobin (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

SURPASS-1 Study Design presents an overview of the SURPASS-1 study design.

Key inclusion and exclusion criteria for the SURPASS-1 study are presented in Key Inclusion and Exclusion Criteria in the SURPASS-1 Study.

In the SURPASS-1 study, at baseline, study participants had a mean

• T2D duration of 4.7 years
• HbA1c of 7.94%
• age of 54.1 years, and
• body mass index (BMI) of 31.9 kg/m².2

In the overall study population, 48% of participants were women.2

Please refer to SURPASS-1: Baseline Demographics and Clinical Characteristics for key baseline demographics and clinical characteristics by treatment arm and total population in SURPASS-1.2

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. In the SURPASS studies, the 

• efficacy estimand evaluates the treatment effect prior to discontinuation of the study drug without confounding effects of antihyperglycemic rescue therapy, and 
• treatment-regimen estimand evaluates the treatment effect irrespective of adherence to the study drug or initiation of rescue antidiabetic drugs.2

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, and
• proportion of participants at HbA1c threshold <7.0% (Primary and Other Secondary Endpoints at Week 40 in SURPASS-1).2
  

In addition, Primary and Other Secondary Endpoints at Week 40 in SURPASS-1 presents the proportion of participants at week 40 at

• HbA1C threshold of ≤6.5%, <5.7%, and
• weight reduction thresholds of ≥5%, ≥10%, and ≥15%.

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.2 

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-1.2

No events of severe or clinically significant hypoglycemia (blood glucose <3.0 mmol/L [54 mg/dL]) were observed in the tirzepatide treatment arms (Hypoglycemia Frequency Through 40 Weeks in SURPASS-1).2