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

Abstract

Aims: The 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 Type 2 diabetes.

Methods: This 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 metformin ± dipeptidyl peptidase-4 inhibitors. Basal insulin was titrated to target pre-breakfast plasma glucose 3.9-4.9 mmol/l.

Results: At end of treatment (104 weeks), mean HbA1c reductions were similar for degludec and glargine; estimated treatment difference between degludec and glargine was 1 mmol/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. 2.05 episodes/patient-year), rates of adverse events possibly or probably related to trial product (0.19 events/patient-year), weight gain (2.7 vs. 2.4 kg) and mean daily insulin doses (0.63 U/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).

Conclusions: In Type 2 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.

Trial registration: ClinicalTrials.gov NCT01193309.

Figure 1

Confirmed hypoglycaemia and glycaemic efficacy in the insulin degludec and glargine groups. (a) Overall confirmed hypoglycaemic episodes. (b) Nocturnal confirmed hypoglycaemic episodes. (c) HbA_1c vs. time. (d) Fasting plasma glucose vs. time. The green box in (c) and (d) on the horizontal axes between weeks 52 and 53 denotes the 1-week basal insulin washout period during which participants switched to NPH and total insulin dose was reduced by 20%. (e) Nine-point profiles of self-monitored blood glucose calibrated to plasma glucose, at baseline (week 0) and after 104 weeks of treatment. Hypoglycaemia data correspond to observed data for the safety analysis set comprising all subjects exposed to treatment. Confirmed hypoglycaemic episodes included either episodes confirmed by self-monitored blood glucose corresponding to plasma glucose value < 3.1 mmol/l or severe episodes requiring assistance. Episodes occurring between 00:01 and 05:59 h (both inclusive) were classified as nocturnal. Glycaemic efficacy data are reported as the mean ± standard error of the mean (sem) for the extension trial set, comprising participants who completed the core trial and entered the extension trial. Missing post-baseline data were imputed using the last-observation-carried-forward approach. Baseline was defined as the time of randomization in the core trial.