Post Hoc Analysis of SURPASS-1 to -5: Efficacy and Safety of Tirzepatide in Adults with Type 2 Diabetes are Independent of Baseline Characteristics.

INTRODUCTION: Newer incretin-based therapies for type 2 diabetes (T2D) have the potential to substantially reduce glycated hemoglobin (HbA1c) and weight with a low associated risk of hypoglycemia. This study aimed to assess the percentage of participants randomized to tirzepatide or comparator who achieved the composite endpoint of HbA1c ≤ 6.5% and weight reduction ≥ 10% without hypoglycemia across prespecified baseline characteristics: T2D duration (≤ 5, > 5-10, or > 10 years), sex, HbA1c (≤ 8.5% or > 8.5%), age (< 65 or ≥ 65 years), and body mass index (< 30, 30 to < 35, or ≥ 35 kg/m). METHODS: This post hoc analysis of SURPASS-1 through -5 evaluated adult study participants with T2D treated with tirzepatide 5, 10, or 15 mg versus placebo or active comparator. Missing HbA1c and weight values were imputed from mixed models for repeated measures. Logistic regression was used to compare tirzepatide versus comparators for the percentage of participants reaching the composite endpoint. RESULTS: Across subgroups, the composite endpoint was achieved by a median of approximately 30%, 45%, and 54% of participants who received tirzepatide 5, 10, and 15 mg, respectively; this was consistent across baseline subgroups, except that a greater percentage of women than men achieved the composite endpoint. The most common treatment-emergent adverse events were gastrointestinal in nature. CONCLUSIONS: In this post hoc analysis, tirzepatide achieved the composite outcome of glycemic control and weight loss with no hypoglycemia, irrespective of baseline characteristics. This may help clinicians as they select suitable treatment in diverse populations. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03954834, NCT03987919, NCT03882970. NCT03730662, and NCT04039503.