Biphasic insulin aspart 30: Literature review of adverse events associated with treatment

Background: Biphasic insulin aspart 30 (BlAsp 30 [30% soluble, rapid-acting insulin aspart and 70% protamine-bound insulin aspart], NovoLog Mix (R) 70/30, Novo Nordisk, Bagsvaerd, Denmark), a premixed insulin analogue, addresses both the prandial and basal aspects of glucose regulation when used once or twice daily in patients with type 1 or type 2 diabetes. It provides overall glycemic control similar to biphasic human insulin 30 (BHI 30, 30% human insulin and 70% neutral protamine Hagedorn [NPH] insulin) in patients with type I or type 2 diabetes. Objective: The aim of this review was to evaluate the safety profile associated with BlAsp 30 In patients with type I or type 2 diabetes versus that of comparator insulin products, including BHI 30 and biphasic insulin lispro 25 (Mix 25 [25% biphasic insulin lispro and 75% protaminated lispro], Humalog (R) Mix 75/25, Ell Lilly and Company, Indianapolis, Indiana), together with the basal insulins, including NPH insulin and insulin glargine (Lantus (R), Sanofi-Aventis Pharmaceuticals, Paris, France). Methods: Data from human clinical studies published in peer-reviewed journals or as conference proceedings that reported safety results in patients with type 1 or type 2 diabetes who were treated with BIAsp 30 versus comparator insulins were evaluated. To locate the appropriate articles, a MEDLINE search was performed for all years up to February 2005, using the following key words: biphasic insulin aspart, BIAsp 30, biphasic insulin, and premixed insulin. Additional papers were identified by examining the reference lists in these papers as well as our own personal reference files. Results from 17 publications were analyzed. The analysis included > 2600 patients with type 2 diabetes (mean [range] age, 58 [36-70] years; duration of diabetes, 11.8 [9-17] years; and baseline glycosylated hemoglobin [HbA(1c)], 8.6% [7.5%-9.9%]). It also included 104 patients with type 1 diabetes (mean [range] age, 44.5 [30-58] years; duration of diabetes, 16 [2-30] years; and baseline HbA(1c), 8.4% [7.2%-10.4%]). Results: Hypoglycemia occurred in 43% to 57% of patients receiving BlAsp 30 versus 32% to 57% of patients receiving BHI 30 and 28% of patients receiving NPH insulin. Major hypoglycemic events were uncommon in most studies; but when they did occur, they were reported less frequently in patients receiving BlAsp 30 (2%-8% of patients) than in patients receiving BHI 30 (2%-14% of patients). Furthermore, patients treated with BlAsp 30 were at lower risk of experiencing minor nocturnal hypoglycemia than patients receiving comparator insulin; in 1 study, the relative risk (BlAsp 30 vs BHI 30) was calculated to be 0.63 (95% Cl, 0.37 to 1.09). The adverse event (AE) profile, weight gain during treatment, and formation of cross-reactive antibodies were not different between BIAsp 30 and BHI 30. AEs were reported in 36% to 90% of patients receiving BlAsp 30, 38% to 88% of patients receiving BHI 30, and 51% of patients receiving Mix 25. The use of oral antidiabetic drugs in combination with BlAsp 30 did not alter the safety profile of BlAsp 30. Conclusion: The flexible and convenient treatment regimen offered by BlAsp 30, together with its ability to improve postprandial glucose control, is associated with a safety profile comparable to that of BHI 30 and NPH insulin, with a lower risk of major and nocturnal hypoglycemic events. (Clin Ther. 2005;27[Suppl B]: S75-S88) Copyright (c) 2005 Excerpta Medica, Inc.