A 32-Week Randomized Comparison of Stepwise Insulin Intensification of Biphasic Insulin Aspart (BIAsp 30) Versus Basal–Bolus Therapy in Insulin-Naïve Patients with Type 2 Diabetes

Introduction: This 32-week, open-label, randomized, parallel-group, multinational trial aimed to compare the efficacy and safety of stepwise insulin intensification of biphasic insulin aspart 30 (BIAsp 30) relative to stepwise intensification of a basal–bolus regimen in insulin-naïve adults with type 2 diabetes (T2D) who continued pretrial treatment with metformin and sulfonylurea. Methods: Adults with T2D were randomized into one of two treatment arms for 32 weeks: (1) BIAsp 30 once daily (OD), with the possibility of stepwise treatment intensification up to BIAsp 30 three times daily (TID); (2) insulin glargine OD, with the possibility of stepwise treatment intensification with insulin aspart up to TID. The primary endpoint was change from baseline in HbA_1c after 32 weeks. Results: After 32 weeks, the estimated mean change in HbA_1c from baseline was statistically significantly lower in the BIAsp 30 arm (− 1.18%) versus basal–bolus (− 1.36%) [estimated treatment difference 0.18%; 95% confidence interval (95% CI) 0.01; 0.36; p < 0.05]. The proportion of patients with HbA_1c below 7.0% was statistically significantly lower with BIAsp 30 (42.9%) compared with basal–bolus (56.9%) (odds ratio 0.58; 95% CI 0.37; 0.89; p = 0.01). The overall rate of severe or blood glucose (BG)-confirmed hypoglycemic events was numerically lower for BIAsp 30 compared with basal–bolus, and a statistically significantly lower rate in nocturnal severe or BG-confirmed hypoglycemia in the BIAsp 30 arm relative to basal–bolus was observed: estimated rate ratio 0.32 (95% CI 0.13; 0.79), p = 0.0131. The proportion of patients with adverse events was similar in both treatment arms. Conclusion: Insulin intensification with BIAsp 30 and basal–bolus showed an improvement in glycemic control; the change in HbA_1c was statistically significantly lower for BIAsp 30 compared to basal–bolus. Basal–bolus treatment was accompanied by a numerically, and statistically significantly, higher rate of overall and nocturnal severe or BG-confirmed hypoglycemia, respectively, compared with BIAsp 30. Funding: Novo Nordisk A/S. Trial Registration: ClinicalTrials.gov identifier, NCT02453685.