Treatment responses to basal insulin glargine 300 U/ml and glargine 100 U/ml in newly defined subphenotypes of type 2 diabetes: A post hoc analysis of the EDITION 3 randomized clinical trial.

Abstract

To compare responses to basal insulin glargine 300 U/ml (IGlar-300) and 100 U/ml (IGlar-100) in newly defined subphenotypes of type 2 diabetes. Insulin-naive participants (n = 858) from the EDITION 3 trial were assigned to subphenotypes 'Mild Age-Related Diabetes (MARD)', 'Mild Obesity Diabetes (MOD)', 'Severe Insulin Resistant Diabetes (SIRD)' and 'Severe Insulin Deficient Diabetes (SIDD)'. Key variables were analysed at baseline and 26 weeks. Participants were comprised of MOD 56.1% (n = 481), SIDD 22.1% (n = 190), MARD 18.2% (n = 156) and SIRD 3.0% (n = 26). After 26 weeks a similar decrease in glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) of 16-19 mmol/mol and 1.4-1.7 mmol/L, respectively, occurred in MARD and MOD with both insulins. SIDD had the most elevated HbA1c and FPG (80-83 mmol/mol/11.1-11.4 mmol/L) and reduction in both HbA1c and FPG was greater with IGlar-100 than with IGlar-300 (-18 vs. -15 mmol/mol and -1.6 vs. -1.3 mmol/L, respectively; each p = .03). In SIDD, despite receiving the highest basal insulin doses, HbA1c decline (57-60 mmol/mol/7.3-7.6%) was suboptimal at week 26. In MOD and SIDD lower incidences with IGlar-300 were found for level 1 nocturnal hypoglycaemia [odds ratio (OR) 0.59, 95% confidence intervals (CI) 0.36-0.97; OR 0.49, 95% CI 0.24-0.99]. In addition, fewer level 2 hypoglycaemia episodes occurred at any time with IGlar-300 in SIDD (OR 0.31, 95% CI 0.13-0.77). Both insulins produce comparable outcomes in type 2 diabetes subphenotypes, but in SIDD, add-on treatment to basal insulin is required to achieve glycaemic targets.