Premixed vs basal-bolus insulin regimen in Type 2 diabetes: comparison of clinical outcomes from randomized...

To evaluate the concordance between data derived from randomized controlled trial (RCT) and real-world estimates of HbA_1c and weight change after 24 weeks of initiation of a basal-bolus compared with a premixed insulin regimen in people with Type 2 diabetes.

Data eight RCTs were pooled after a systematic review of studies examining basal-bolus (n = 1893) or premixed (n = 1517) regimens. Real-world data were extracted from the UK primary care dataset for people on basal-bolus (n = 7483) or premixed insulin regimens (n=10 744). The mean differences between HbA_1c and weight from baseline were calculated using t-tests, while analysis of variance was used to compare the two treatment regimens. Linear regression analyses were used to determine the predictors of this change.

Both insulin regimens were associated with HbA_1c reductions (real-world data -0.28%; RCT data, -1.4%) and weight gain (real-world data, +0.27 kg; RCT data, +2.96 kg) but there were no significant differences between basal-bolus and premixed insulin. Discordances in the pattern of treatment response were observed, however, between real-world and RCT data for both insulin regimens. For any given baseline HbA_1c concentration, the change in HbA_1c in the RCTs was greater than in real-world conditions and for those with baseline weight above ~60 kg, RCT data showed overall weight gain in contrast to slight weight loss in the real-world population. Lastly, for both randomized controlled trial and real-world populations, while greater baseline weight was associated with reduced response to treatment, the association was much steeper in the RCT than in the real-world population. In addition, greater baseline weight was associated with greater weight reductions in both premixed insulin and basal-bolus insulin regimens, although to a lesser extent with the latter.

These results highlight specific discrepancies in the HbA_1c reduction and weight change in insulin regimen between real world versus RCT populations; with greater reduction in HbA_1c and greater increase in weight observed in the RCT population than in the real-world population. Also, the basal-bolus regimens in both real-world and RCT populations showed greater reduction in HbA_1c compared to the premix regimen (though more marked in RCTs), while the premix regimen showed greater increase in weight in real-world, as against basal-bolus in the RCT population.