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 nonsignificant 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.