Starting insulin therapy with basal insulin analog or premix insulin analog in T2DM: a pooled analysis of treat-to-target trials

Objective: Although the choice of starting insulin for people with type 2 diabetes mellitus (T2DM) is often a basal or premix insulin analog, there is little evidence to base this decision on. This analysis aimed to determine if measurable clinical characteristics prior to starting insulin could predict differences in improved glycemic control between these options. Research design and methods: A thorough literature search was performed for treat-to-target studies in insulin-naive individuals with T2DM treated with biphasic insulin aspart (BIAsp 30), a basal insulin analog (insulin glargine or insulin detemir) or NPH insulin regimens once or twice daily plus oral glucose-lowering drugs (OGLDs). Patient data were pooled and mean baseline age, diabetes duration, gender, body mass index (BMI), HbA(1c), fasting plasma glucose (FPG), average postprandial plasma glucose over three meals (PPG) and bedtime PG were investigated for prediction of improved HbA(1c), FPG or PPG. Statistical analyses employed a linear mixed model with insulin type, OGLD, time and time-squared as fixed effects and patient and trial as random effects. Results: Baseline age (p = 0.022) and bedtime PG (p = 0.036) were inter-related predictors of HbA1c. In older individuals with higher bedtime PG, BIAsp 30 appeared to be more beneficial. In contrast, basal insulin appeared to be a better choice in younger individuals with lower bedtime PG. For FPG, BMI (p = 0.011) and post-breakfast PG (p = 0.042) were identified as predictors. Basal insulin appeared to achieve better FPG in patients with lower BMI and higher post-breakfast PG, while BIAsp 30 appeared to be better in patients with higher BMI and lower post-breakfast PG. Age (p = 0.0347) was the only baseline characteristic associated with differences in average PPG: mean PPG was similar between regimens in younger people, but BIAsp 30 achieved better PPG results in older persons. Minor hypoglycemia was reported by 56% of BIAsp 30- and 45% of basal-treated individuals. The major limitation of the study was that only Novo Nordisk trials were included in the analysis as access to individual patient data was required. As the trials were fairly heterogeneous a strict methodology was used to minimize potential confounding factors. Conclusions: Premix analog rather than basal insulin may be an appropriate choice to target HbA1c values in older individuals and those with higher bedtime PG, while basal insulin may be more appropriate to target FPG in patients with lower BMI and higher post-breakfast PG.