Tirzepatide as an Add-on for Participants with Inadequate Glycemic Control Using Basal Insulin: Pooled Subgroup Analysis of SURPASS-5 and -6.

INTRODUCTION: This study aimed to assess the efficacy and hypoglycemia safety of tirzepatide as an add-on to basal insulin in people with inadequate glycemic control, across subgroups of baseline age, type 2 diabetes (T2D) duration, HbA1c, and basal insulin dosage using pooled data from the SURPASS-5 and -6 studies. METHODS: This exploratory post hoc analysis compared data from 1072 participants treated with tirzepatide as an add-on to basal insulin in SURPASS-5 and SURPASS-6. In SURPASS-5, tirzepatide was compared against placebo, while in SURPASS-6, it was compared with insulin lispro. Insulins were titrated to the target in both trials. Subgroups were divided by baseline HbA1c (≤ 8.5% and > 8.5%), age (< 65 years and ≥ 65 years), duration of T2D (< 10 years and ≥ 10 years), and insulin glargine dose (< 50 IU/day and ≥ 50 IU/day). RESULTS: At the primary endpoint, tirzepatide added to basal insulin glargine was associated with significant reductions in HbA1c, fasting serum glucose, and insulin glargine dose across all subgroups (P < 0.001), with no significant heterogeneity (all interaction P values > 0.1). Clinically significant hypoglycemia incidence rates were highest in younger participants with a baseline HbA1c above 8.5% and duration of T2D ≥ 10 years. CONCLUSIONS: In this study, tirzepatide combined with basal insulin glargine was associated with reductions in HbA1c, fasting serum glucose, and insulin glargine dose from baseline, with a low incidence of hypoglycemia, regardless of baseline age, HbA1c, duration of T2D, or basal insulin dose. TRIAL REGISTRATION: Trials were registered at ClinicalTrials.gov under the identifiers NCT04039503 (SURPASS-5) and NCT04537923 (SURPASS-6).