Lower rates of hypoglycemia during maintenance treatment with insulin degludec/insulin aspart versus biphasic insulin aspart 30: a combined analysis of two Phase 3a studies in type 2 diabetes

Background Insulin degludec/ insulin aspart(IDegAsp) is a soluble coformulation of the basal analog insulin degludecand the rapid-acting prandial insulin aspartin a single injection. The present combined analysis of two Phase 3a trials compared the incidence of hypoglycemiain participants treated twice daily with IDegAsp or biphasic insulin aspart30 (BIAsp 30). Methods Hypoglycemiadata were analyzed from two similarly designed randomized controlled open-label treat-to-target Phase 3a clinical trials of adults with type 2 diabetes (T2D). Participants were treated twice daily with IDegAsp or BIAsp 30, with breakfast and their main evening meal. Results Over 26 weeks, the rates of overall confirmed, nocturnalconfirmed and severe hypoglycemic events were 19%, 57%, and 39% lower, respectively, with IDegAsp (n = 504) than BIAsp 30 (n = 364); estimated rate ratios were 0.81 (95% confidence interval [CI] 0.67, 0.98; P = 0.0341), 0.43 (95% CI 0.31, 0.59; P = 0.0001), and 0.61 (95% CI 0.26, 1.45; P = NS). The between-treatment differences were more pronounced during the maintenance period (≥16 weeks); compared with BIAsp 30, rates of overall confirmed, nocturnalconfirmed and severe hypoglycemic events with IDegAsp were 0.69 (95% CI 0.55, 0.87; −31%; P = 0.0015); 0.38 (95% CI 0.25, 0.58; −62%; P < 0.0001), and 0.16 (95% CI 0.04, 0.59; −84%; P = 0.0061), respectively. Conclusions Compared with BIAsp 30 twice daily, IDegAsp twice daily provided similar improvements in glycemic control with a lower risk of hypoglycemia, particularly nocturnal hypoglycemia, in subjects with T2D previously treated with insulin.