Comparison of insulin degludec with insulin glargine in insulin-naive subjects with Type 2 diabetes: a 2-year randomized, treat-to-target trial

AimsThe aim of this study was to compare long-term safety and efficacy of the basal insulin analogue degludec with glargine in insulin-naive subjects with Type2 diabetes. MethodsThis open-label trial included a 52-week core period followed by a 52-week extension. Participants were randomized 3:1 to once-daily degludec or glargine, administered with metformindipeptidyl peptidase-4 inhibitors. Basal insulin was titrated to target pre-breakfast plasma glucose 3.9-4.9mmol/l. ResultsAt end of treatment (104weeks), mean HbA(1c) reductions were similar for degludec and glargine; estimated treatment difference between degludec and glargine was 1mmol/mol (95%CI -1 to 3) [0.07% (95%CI -0.07 to 0.22)], P=0.339 in the extension trial set (degludec 551, glargine 174), comprising subjects who completed core trial and continued into the extension trial. Overall confirmed hypoglycaemia rates (1.72 vs. 2.05episodes/patient-year), rates of adverse events possibly or probably related to trial product (0.19events/patient-year), weight gain (2.7 vs. 2.4kg) and mean daily insulin doses (0.63U/kg) were similar between treatments in the safety analysis set (degludec 766, glargine 257) comprising all treated subjects. Rates of nocturnal confirmed hypoglycaemia (0.27 vs. 0.46 episodes/patient-year; P=0.002) and severe hypoglycaemia (0.006 vs. 0.021 episodes/patient-year, P=0.023) were significantly lower with degludec for the safety analysis set (analysis based on intention-to-treat full analysis set comprising all randomized subjects). ConclusionsIn Type2 diabetes, insulin degludec in combination with oral anti-diabetic drugs, safely and effectively improves long-term glycaemic control, with a significantly lower risk of nocturnal hypoglycaemia as compared with glargine. What's new? Insulin degludec, a basal insulin analogue, uses a novel protraction mechanism, resulting in a flat, stable profile and a duration of action greater than 42h. Consistent with its pharmacokinetic and pharmacodynamic profile, insulin degludec in combination with oral anti-diabetic drugs provided long-term glycaemic control similar to insulin glargine with a lower risk for nocturnal hypoglycaemia in insulin-naive patients with Type2 diabetes, in a 1-year, randomized study. This extension study reports 2-year data, confirming that insulin degludec in combination with oral anti-diabetic drugs maintains stable glycaemic control with a sustained benefit in reducing hypoglycaemic risk in Type2 diabetes.