Background: It is estimated that 39% of people with diabetes worldwide who use insulin are prescribed premixes, largely because of the practical advantages of addressing both prandial and basal insulin needs with a single product. Rapid-acting premixed insulin analogues such as biphasic insulin aspart 30 (BIAsp 30 [30% soluble insulin aspart and 70% protamine-crystallized insulin aspart], NovoLog Mix 70/30, Novo Nordisk, Bagsvaerd, Denmark) have been developed recently to overcome the pharmacokinetic limitations of regular human insulin used in the most commonly prescribed premix, biphasic human insulin 30 (BHI 30, 30% human insulin and 70% neutral protamine Hagedorn [NPH] insulin). It would be expected that these pharmacokinetic improvements would enhance clinical performance. However, the efficacy of BIAsp 30 compared with other common treatment regimens has not yet been systematically reviewed.
Objective: The aim of this paper is to review current data on the efficacy of BIAsp 30 in comparison with other treatment strategies in type 2 diabetes, including oral antidiabetic drugs (eg, metformin, sulfonylureas, meglitinides, thiazolidinediones), conventional insulins (eg, BHI 30, NPH insulin), and other analogue insulins (eg, insulin glargine, biphasic insulin lispro 25 [Mix 25, 25% biphasic insulin lispro and 75% protaminated lispro]). The focus will be on comparative efficacy (ie, postprandial glucose [PPG], blood glucose profiles, and glycosylated hemoglobin [HbA1c]).
Methods: We identified human clinical studies published through February 2005 involving BIAsp 30 in patients with type 2 diabetes by performing a MEDLINE search (key words: biphasic insulin aspart, BIAsp 30, biphasic insulin, and premixed insulin). Additional papers were identified by assessing (1) the reference lists in these studies, (2) published conference proceedings, and (3) our reference files. A total of 21 relevant papers were retrieved: 13 were published as full manuscripts, 1 as a short communication, 5 as abstracts, and 1 as a poster. One paper is currently in press. Novo Nordisk supplied data from an unpublished trial (Study 1536, 2004), as well as data from a trial published in abstract form only (Study 1269, 2002).
Results: A regimen of BIAsp 30 BID, at breakfast and dinner, provides improved PPG control compared with BHI 30 BID, NPH BID, and insulin glargine OD for patients with type 2 diabetes. Fasting plasma glucose (FPG) with BIAsp 30 was not significantly different from FPG with insulin glargine; however, FPG was higher with BIAsp 30 than with NPH. BIAsp 30 prevented excessive PPG excursions whether it was injected at the beginning of a meal or < or =15 minutes after starting a meal. BIAsp 30 was not associated with an increased risk of major hypoglycemia compared with other insulin regimens used in the studies reviewed. The incidence of minor hypoglycemic events with BIAsp 30 varied across studies but occurred with frequency or risk similar to BHI 30, Mix 25, or NPH. Treat-to-target trials reported that BIAsp 30 can be used to intensify insulin therapy and to reach the glycemic target recommended by the American Diabetes Association (ie, HbA1c <7.0%). One study reported a greater lowering of postprandial triglyceride levels with BIAsp 30 than with BHI 30.
Conclusions: BIAsp 30 BID can reduce PPG levels to a greater extent than other common treatment regimens, including basal insulin OD. Using BIAsp 30, even once daily, may allow some patients to reach glycemic targets with a degree of convenience and tolerability that may not be achievable with other treatment regimens.