Efficacy and safety of three-times-daily versus twice-daily biphasic insulin aspart 30 in patients with type 2 diabetes mellitus inadequately controlled with basal insulin combined with oral antidiabetic drugs.

Abstract Aims To compare the efficacy and safety of biphasic insulin aspart 30 (BIAsp 30) administered three times daily (TID) vs. twice daily (BID), plus metformin, in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on basal insulin ± 1 oral antidiabetic drug (OAD). Methods Randomised, multinational, open-label, treat-to-target trial. Subjects inadequately controlled (HbA1c 7.5–10.0%) on basal insulin and metformin ± 1 OAD were randomised to BIAsp 30 TID ( n  = 220) or BIAsp 30 BID ( n  = 217). Primary endpoint was change from baseline in HbA1c after 24 weeks of treatment. Results Most (400/437, 91.5%) subjects completed the trial. The majority (276/400 [69.0%]) were from the China region. After 24 weeks, HbA1c decreased comparably in both BIAsp 30 groups (−1.7% vs. −1.6% [–19 vs. –18 mmol/mol], for TID and BID dosing, respectively; estimated treatment difference: –0.09% [−0.23; 0.06] 95% CI , –1 mmol/mol [−3; 1], p =  0.26). Safety profiles, including number of subjects experiencing hypoglycaemia, were similar. Conclusions BIAsp 30 administered either TID or BID with metformin was a safe and effective option when intensifying treatment after failure of basal insulin and OADs in patients with T2DM. Adding a third injection at lunchtime may be preferable if HbA1c remains above target, if the lunchtime meal is the largest meal of the day, or if persistent postprandial hyperglycaemia after lunch is observed. Trial registration number: ClinicalTrials.gov , NCT02582242.