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

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-naive type 2 diabetes mellitus (T2DM(insulin-naive)), 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-naive). Total daily insulin dose was significantly lower with degludec in T1DM(B/B) and T2DM(insulin-naive). Estimated hypoglycemia rate ratios for degludec/glargine were as follows for T1DM(B/B), T2DM(insulin-naive) and T2DM(B/B), respectively: non-severe nocturnal 0.83,0.64, 0.75 (all P < 0.05); non-severe daytime 1.14 [not significant (ns)], 0.89 (ns), and 0.83 (P < 0.05). Rate ratios for severe events were 1.12 (ns) (T1DM(B/B)); 0.14 ( P < 0.05) ( T2DM(insulin-naive)); 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-naive), degludec is also associated with significantly greater reductions in FPG and lower total doses of insulin versus glargine.