Premixed insulin regimens for type 2 diabetes.

Abstract

Type 2 diabetes mellitus is a disease characterized by progressive b-cell failure, and many patients will eventually require insulin therapy to maintain glycemic control [1]. Premixed (biphasic) insulin regimens are an insulin treatment scheme prescribed both in insulin-naive patients and insulin-treated patients who need further treatment intensification [2, 3]. Alternative options include basal insulin for initiating insulin therapy and basal-plus or basal-bolus regimens for insulin treatment intensification. There is currently no unanimous guidance regarding the role of premixed insulin regimens as opposed to other types of insulin, both for initiating and for intensifying insulin therapy in type 2 diabetes. The American Diabetes Association and the European Association for the Study of Diabetes suggest initiation therapy with basal insulin and consider premixed regimens only as intensification therapy in selected patients [4]. Conversely, the International Diabetes Federation recommends beginning insulin therapy with either basal insulin once daily or biphasic insulin once or twice daily [5], while the National Institute for Health and Care Excellence in the United Kingdom considers both basal insulin and premixed regimens as secondary options to human NPH insulin for initiating insulin therapy [6]. In a meta-analysis by Giugliano et al. published in this issue, overall, there was no difference in HbA1c lowering between premixed insulin and basal-bolus insulin regimens, including a subgroup analysis comparing variable premixed insulin with variable basal-bolus regimens [7]. How do these data compare to findings from recent individual trials and existing meta-analyses? For insulin-naive patients, several meta-analyses have explored the efficacy of premixed insulin against basal, basal-plus, or basal-bolus insulin regimens. In a metaanalysis of five randomized controlled trials (RCTs) in insulin-naive patients, biphasic insulin was associated with greater reductions in HbA1c compared to basal insulin (weighted mean difference -0.45 %; 95 % confidence interval -0.70 to -0.19) [8]. Likewise, a more recent meta-analysis demonstrated that treatment with biphasic insulin aspart 30 (aspart/aspart protamine 30/70) once or twice daily resulted in better glycemic control in comparison with insulin glargine once daily (-0.21 %; -0.35 to -0.08) [9]. Similarly, the recently published GALAPAGOS study demonstrated that in insulin-naive patients, premixed insulin once or twice daily reduced HbA1c by a further 0.16 % (confidence interval 0.04 to 0.27) compared with insulin glargine with or without insulin glulisine [10]. Finally, in a subgroup analysis in insulin-naive patients, premixed regimen had no difference with basal-bolus regimens (-0.15 %; -0.52 to 0.22) [11]. For patients already on basal insulin, results from the LanScape study suggested that basal-plus regimens (glargine plus insulin glulisine once daily) are non-inferior to premixed insulin (biphasic insulin aspart 30 twice daily) in reducing HbA1c [12]. However, a recent meta-analysis by Wang et al. concluded that basal-bolus regimens have superior glycemic efficacy to premix insulin in non-insulinnaive patients (-0.22 %; -0.42 to -0.02) [11]. Findings & Apostolos Tsapas atsapas@auth.gr