Lower hypoglycemia rates with insulin degludec compared to insulin glargine: Data from a prospectively planned meta-analysis

Introducution: Insulin degludec (IDeg) is a new basal insulin that forms soluble multihexamers after sc injection. Ideg has long and stable glucose-lowering effect. Methods: The objective of this pre-specified analysis was to compare the rate of hypoglycemia with IDeg vs. IGlar across trials. Hypoglycemia was defined as follows: self-reported confirmed hypoglycaemia = PG< 56 mg/dL or severe hypoglycemia (requiring assistance) nocturnal confirmed hypoglycaemia = 00:01 – 05:59 incl. Rates were analyzed with a negative binomial regression model on patient level data. In the analysis all open-labeled, randomized, treat-to-target phase 3a trials of 26 or 52 weeks were included in which once-daily IDeg (n = 2899) was compared to IGlar (n = 1431) in T1DM (2 trials) and T2DM (5 trials). Results: IDeg showed statistically significantly lower rates for nocturnal hypoglycemia compared to IGlar for the pooled population of type 1 and 2 diabetes and for overall hypoglycemia in T2DM (Table). More pronounced benefits of Ideg could be revealed in analyses of the maintenance period (stable glycemia and insulin dose [obtained from 16 weeks onward]). Additional heterogeneity analysis revealed significantly less risk of severe hypoglycemia with IDeg vs. IGlar in insulinnaïve T2DM (rate ratio 0.14 [0.03; 0.70] 95% CI). Conclusion: This meta-analysis showed significantly lower rates especially for nocturnal hypoglycemia than IGlar at similar levels of A1C for Ideg compared to Iglar. Therefore treatment with Ideg may provide clinical advantages for patients. Table 1: Metaanalysis of confirmed hypoglycemia Rate overall hypoglycemia (Ideg/Iglar) Rate nocturnal hypoglycemia (Ideg/Iglar) Complete study Maintenance period Complete study Maintenance period T2DM 0.83 [0.74; 0.94]* 0.75 [0.66; 0.87]* 0.68 [0.57; 0.82]* 0.62 [0.49; 0.78]* T2DM-insulinnaive 0.83 [0.70; 0.98]* 0.72 [0.58; 0.88]* 0.64 [0.48; 0.86]* 0.51 [0.36; 0.72]* T1DM 1.10 [0.96; 1.26] 1.02 [0.88; 1.19] 0.83 [0.69; 1.00]* 0.75 [0.60; 0.94]* T1DM +T2DM 0.91 [0.83; 0.99]* 0.84 [0.75; 0.93]* 0.74 [0.65; 0.85]* 0.68 [0.58; 0.80]*