Twice-daily insulin degludec/insulin aspart provides superior fasting plasma glucose control and a reduced rate of hypoglycaemia compared with biphasic insulin aspart 30 in insulin-naïve adults with Type 2 diabetes

Aim To evaluate the efficacy and safety of twice‐daily insulin degludec/insulin aspart vs. twice‐daily biphasic insulin aspart 30 in people with Type 2 diabetes mellitus who were naïve to insulin. Methods In this 26‐week, multinational, open‐label, controlled, two‐arm, parallel‐group, treat‐to‐target trial, participants [mean (± sd) age 58.9 (±8.9) years, duration of diabetes 9.5 (±5.9) years, HbA1c 68 (±8.7) mmol/mol or 8.4 (±0.8)% and BMI 31.2 (±4.2) kg/m2) were randomized (1:1) to insulin degludec/insulin aspart (n = 197) or biphasic insulin aspart 30 (n = 197), administered with breakfast and the main evening meal, titrated to a self‐monitored plasma glucose target > 3.9 and ≤ 5.0 mmol/l. Results The mean HbA1c was reduced to 49 mmol/mol (6.6%) with insulin degludec/insulin aspart and 48 mmol/mol (6.5%) with biphasic insulin aspart 30. Insulin degludec/insulin aspart achieved the prespecified non‐inferiority margin (estimated treatment difference 0.02%; 95% CI −0.12, 0.17). Insulin degludec/insulin aspart was superior in lowering fasting plasma glucose (estimated treatment difference −1.00 mmol/l; 95% CI −1.4, −0.6; P < 0.001) and reducing overall and nocturnal confirmed hypoglycaemia at a similar overall insulin dose compared with biphasic insulin aspart 30. Similar proportions of participants in each arm experienced severe hypoglycaemia. Adverse events were equally distributed. Conclusions Consistent with previous findings, insulin degludec/insulin aspart twice daily effectively improved long‐term glycaemic control, with superior reductions in FPG, and significantly less overall and nocturnal confirmed hypoglycaemia compared with biphasic insulin aspart 30 in people with Type 2 diabetes who were insulin‐naïve. What's new? Insulin degludec/insulin aspart (IDegAsp) is the first soluble co‐formulation that combines two insulin analogues. It provides effective basal and prandial glycaemic coverage. This trial aimed to compare twice‐daily IDegAsp and twice‐daily biphasic insulin aspart 30 (BIAsp 30) in people with Type 2 diabetes mellitus who were naïve to insulin. IDegAsp achieved the prespecified non‐inferiority margin for HbA1c and was superior to BIAsp 30 in lowering fasting plasma glucose and overall and nocturnal confirmed hypoglycaemia at a similar insulin dose compared with BIAsp 30. The results of this study indicate that IDegAsp provides an effective means of initiating insulin treatment with a marked reduction in hypoglycaemia in people with Ty