Insulin degludec/insulin aspart once daily in Type 2 diabetes: a comparison of simple or stepwise titration...

To compare the efficacy and safety of two titration algorithms for insulin degludec/insulin aspart (IDegAsp) administered once daily with metformin in participants with insulin-naïve Type 2 diabetes mellitus.

This open-label, parallel-group, 26-week, multicentre, treat-to-target trial, randomly allocated participants (1:1) to two titration arms. The Simple algorithm titrated IDegAsp twice weekly based on a single pre-breakfast self-monitored plasma glucose (SMPG) measurement. The Stepwise algorithm titrated IDegAsp once weekly based on the lowest of three consecutive pre-breakfast SMPG measurements. In both groups, IDegAsp once daily was titrated to pre-breakfast plasma glucose values of 4.0-5.0 mmol/l. Primary endpoint was change from baseline in HbA_1c (%) after 26 weeks.

Change in HbA_1c at Week 26 was IDegAsp_Simple -14.6 mmol/mol (-1.3%) (to 52.4 mmol/mol; 6.9%) and IDegAsp_Stepwise -11.9 mmol/mol (-1.1%) (to 54.7 mmol/mol; 7.2%). The estimated between-group treatment difference was -1.97 mmol/mol [95% confidence interval (CI) -4.1, 0.2] (-0.2%, 95% CI -0.4, 0.02), confirming the non-inferiority of IDegAsp_Simple to IDegAsp_Stepwise (non-inferiority limit of ≤ 0.4%). Mean reduction in fasting plasma glucose and 8-point SMPG profiles were similar between groups. Rates of confirmed hypoglycaemia were lower for IDegAsp_Stepwise [2.1 per patient years of exposure (PYE)] vs. IDegAsp_Simple (3.3 PYE) (estimated rate ratio IDegAsp_Simple /IDegAsp_Stepwise 1.8; 95% CI 1.1, 2.9). Nocturnal hypoglycaemia rates were similar between groups. No severe hypoglycaemic events were reported.

In participants with insulin-naïve Type 2 diabetes mellitus, the IDegAsp_Simple titration algorithm improved HbA_1c levels as effectively as a Stepwise titration algorithm. Hypoglycaemia rates were lower in the Stepwise arm.