Intensification of insulin therapy with basal-bolus or premixed insulin regimens in type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials

The purpose of this study was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the effect of intensified insulin regimens (basal-bolus versus premixed) on glycemic control in patients with type 2 diabetes. We conducted an electronic search until March 2015 on many electronic databases including online registries of ongoing trials. All RCTs comparing basal-bolus with premixed insulin regimens, with a duration of >12 weeks and with >30 patients per arm, were included. Investigators extracted data on study characteristics, outcome measures, and methodological quality. We found thirteen RCTs lasting 16–60 weeks and involving 5255 patients assessed for the primary endpoint (reduction of HbA1c from baseline). Meta-analysis of change in HbA1c level between basal-bolus and premixed insulin regimens resulted in a small and non-significant difference of 0.09 % (95 % CI −0.03 to 0.21), with substantial heterogeneity between studies (I ² = 74.4 %). There was no statistically significant difference in the event rate for overall hypoglycemia (0.16 episode/patient/year, 95 %CI −2.07 to 2.3), weight change (−0.21 kg, −0.164 to 0.185), and daily insulin dose (−0.54 U/day, −2.7 to 1.6). The likelihood for reaching the HbA1c <7 % was 8 % higher (3–13 %, I ² = 68.8 %) with the basal-bolus as compared with the premixed regimen. There is no clinically relevant difference in the efficacy of basal-bolus versus premixed insulin regimens for HbA1c decrease in type 2 diabetic patients. These findings may be helpful to adapt treatment to individual patient needs.