Responses to Basal Insulin Glargine (300 U/mL and 100 U/mL) with or Without Pre-prandial Insulin in Pre-treated Subphenotypes of Type 2 Diabetes: Insights from a Post Hoc Analysis.

ABSTRACT

INTRODUCTION: This study aimed to evaluate glycemic outcomes in subphenotypes of type 2 diabetes (T2D) with HbA1c > 7.0%, previously on basal insulin (pre-BI) alone (≥ 42 U/day) or on basal-bolus therapy (pre-BB), and who were switched to either basal insulin glargine 300 U/mL (IGlar-300) or 100 U/mL (IGlar-100), with or without pre-prandial insulin. METHODS: Participants from EDITION 2 (pre-BI, n = 785), and EDITION 1 (pre-BB, n = 792) trials were assigned retrospectively to subphenotypes of T2D severe insulin deficient diabetes (SIDD), mild age-related diabetes (MARD), mild obesity diabetes (MOD), and severe insulin resistant diabetes (SIRD). Key efficacy and safety parameters were analyzed at baseline, and after 26 weeks, for IGlar-300 and IGlar-100 pooled groups according to subphenotypes. Outcomes were also compared with insulin-naïve subphenotypes on oral antihyperglycemic drugs (OADs) from the EDITION 3 trial (pre-OAD, n = 858). RESULTS: Pre-BI and pre-BB treated subphenotypes with SIDD had a higher mean HbA1c (8.9% and 9.1%) at baseline compared to those of MARD (7.7% and 7.8%) and MOD (8.1% and 8.2%) and after 26 weeks remained above target HbA1c (7.7% and 8.0%) despite mean glargine doses of 0.7 to 1.0 U/kg/day and pre-prandial insulin use in the pre-BB SIDD subgroup. Pre-BB treated individuals with MARD and MOD achieved lower HbA1c levels (6.9% and 7.2%) than the pre-BI groups (7.3% and 7.5%) despite similar mean FPG levels (123-130 mg/dL). Only 19-22% of participants with SIDD achieved HbA1c < 7.0% compared to 33-51% with MARD and MOD, respectively. Pre-BI and pre-BB treated subphenotypes experienced more hypoglycemia than pre-OAD treated subphenotypes. CONCLUSION: Individuals with T2D assigned post hoc to the SIDD subphenotype achieved suboptimal glycemic control with glargine regimens including basal-bolus therapy, alerting clinicians to improve further diabetes treatment, particularly post-prandial glycemic control, in individuals with SIDD.