Insulin Degludec Versus Insulin Glargine in Type 1 and Type 2 Diabetes Mellitus: A Meta-Analysis of Endpoints in Phase 3a Trials

摘要

Introduction Insulin degludec (degludec) is a basal insulin with an ultra-long, stable action profile and reduced pharmacodynamic variability. Seven phase 3a trials compared degludec with insulin glargine (glargine). Patient-level meta-analyses were performed to obtain a comprehensive overview of differences between the insulin preparations, possible because consistent outcome definitions were utilized. Methods Three categories of trials were analyzed: basal–bolus-treated type 1 diabetes mellitus (T1DM_B/B), insulin-na?ve type 2 diabetes mellitus (T2DM_{insulin-na?ve}), and basal–bolus-treated T2DM (T2DM_B/B). Regression models were adjusted for baseline characteristics. Endpoints analyzed were glycosylated hemoglobin (HbA_1c), fasting plasma glucose (FPG), insulin dose and hypoglycemic rates analyzed in mutually exclusive groups: non-severe nocturnal, non-severe daytime, and severe. Results As with previous treat-to-target trials, reductions in HbA_1c were similar between degludec and glargine. Reductions in FPG were significantly greater with degludec in T1DM_B/B and T2DM_{insulin-na?ve}. Total daily insulin dose was significantly lower with degludec in T1DM_B/B and T2DM_{insulin-na?ve}. Estimated hypoglycemia rate ratios for degludec/glargine were as follows for T1DM_B/B, T2DM_{insulin-na?ve} and T2DM_B/B, respectively: non-severe nocturnal 0.83, 0.64, 0.75 (all P B/B); 0.14 ( P insulin-na?ve); and not analyzed (T2DM_B/B) due to too few events. Conclusions Compared with glargine, degludec is associated with equivalent HbA_1c control and significantly lower nocturnal hypoglycemia rates. In T1DM_B/B and T2DM_{insulin-na?ve}, degludec is also associated with significantly greater reductions in FPG and lower total doses of insulin versus glargine.