Insulin Degludec Once-Daily in Type 2 Diabetes: Simple or Step-Wise Titration (BEGIN: Once Simple Use)

INTRODUCTION: Insulin degludec (IDeg) is a new basal insulin in development with a flat, ultra-long action profile that may permit dosing using a simplified titration algorithm with less frequent self-measured blood glucose (SMBG) measurements and more simplified titration steps than currently available basal insulins. METHODS: This 26-week, multi-center, open-label, randomized, treat-to-target study compared the efficacy and safety of IDeg administered once-daily in combination with metformin in insulin-naïve subjects with type 2 diabetes using two different patient-driven titration algorithms: a “Simple” algorithm, with dose adjustments based on one pre-breakfast SMBG measurement (n = 111) versus a “Step-wise” algorithm, with adjustments based on three consecutive pre-breakfast SMBG values (n = 111). IDeg was administered using the FlexTouch(®) insulin pen (Novo Nordisk A/S, Bagsværd, Denmark), with once-weekly dose titration in both groups. RESULTS: Glycosylated hemoglobin (HbA(1c)) decreased from baseline to week 26 in both groups (−1.09%, IDeg(Simple); −0.93%, IDeg(Step-wise)). IDeg(Simple) was non-inferior to IDeg(Step-wise) in lowering HbA(1c) [estimated treatment difference (IDeg(Simple) − IDeg(Step-wise)): −0.16% points (−0.39; 0.07)(95% CI)]. Fasting plasma glucose was reduced (−3.27 mmol/L, IDeg(Simple); −2.68 mmol/L, IDeg(Step-wise)) with no significant difference between groups. Rates of confirmed hypoglycemia [1.60, IDeg(Simple); 1.17, IDeg(Step-wise) events/patient year of exposure (PYE)] and nocturnal confirmed hypoglycemia (0.21, IDeg(Simple); 0.10, IDeg(Step-wise) events/PYE) were low, with no significant differences between groups. Daily insulin dose after 26 weeks was 0.61 U/kg (IDeg(Simple)) and 0.50 U/kg (IDeg(Step-wise)). No significant difference in weight change was seen between groups by week 26 (+1.6 kg, IDeg(Simple); +1.1 kg, IDeg(Step-wise)), and there were no clinically relevant differences in adverse event profiles. CONCLUSION: IDeg was effective and well tolerated using either the Simple or Step-wise titration algorithm. While selection of an algorithm must be based on individual patient characteristics and goals, the ability to attain good glycemic control using a simplified titration algorithm may enable patient empowerment through self-titration, improved convenience, and reduced costs.