Importance of targeting post-prandial hyperglycaemia to achieve HbA1c goals in insulin glargine-treated subphenotypes of type 2 diabetes

Abstract

Aims: To explore outcome parameters related to achieving HbA1c goal (<7.0%) in subphenotypes of type 2 diabetes (T2D), either on basal insulin (BI) glargine 300 U/mL or 100 U/mL or switched to these BIs (≥42 U/day) alone or with pre-prandial insulin. Materials and Methods: Participants from three EDITION T2D trials (n = 2,435) were clustered into T2D subphenotypes, with ≥97% having either Severe Insulin-Deficient Diabetes (SIDD) (9%–22%), Mild Age-Related Diabetes (MARD) (8%–18%), or Mild Obesity Diabetes (MOD) (56%–78%) across trials. Subphenotypes were stratified by HbA1c goal achievement (HbA1c <7.0%/responders or ≥7.0%/non-responders), and efficacy and safety parameters were analysed both at baseline and after 26 weeks. Glargine groups were pooled. Results: With all basal insulin regimens, the responders were fewest in SIDD (19%–33%), followed by MOD (33%–56%) and MARD (42%–62%). Mean FPG at 26 weeks was slightly lower in responders (103–128 mg/dL; 5.8–7.1 mmol/L) compared to non-responders (124–143 mg/dL; 6.9–7.9 mmol/L) in each subphenotype, despite equivalent or higher mean glargine doses in non-responders. Self-monitored post-prandial glucose (PPG) was consistently above the recommended target of 140 mg/dL (7.8 mmol/L) in non-responders, even in those on intensified insulin treatment. Hypoglycaemia risk was similar or only slightly increased in responders compared to non-responders across subphenotypes. Conclusions: With glargine-based regimens, strict control of PPG is necessary to attain HbA1c <7.0% across all T2D subphenotypes. Therefore, to achieve optimal treatment goals, especially in the SIDD subphenotype, appropriate dose adjustments of both basal and preprandial insulin are required.