Less Nocturnal Hypoglycemia for Insulin Degludec vs. Insulin Glargine in Subjects with T1DM and Baseline A1c of 7.5–8.5%: A Meta-Analysis

Abstract

The risk of hypoglycemia increases as A1c levels approach recommended targets. Insulin degludec (IDeg) is a new basal insulin that forms soluble multi-hexamers upon injection, resulting in an ultra-long action profile. We analyzed whether IDeg allows improved glycemic control together with lower rates of hypoglycemia vs. insulin glargine (IGlar) in T1DM patients with baseline A1c 7.5–8.5%. Changes in A1c and fasting plasma glucose (FPG) and rates of hypoglycemia were analyzed with linear models. Hypoglycemia was defined as rates of self-reported confirmed hypoglycemia (PG<[3.1 mmol/L] 56 mg/dL or severe episodes requiring assistance) and nocturnal confirmed hypoglycemia (onset 00:01–05:59h, inclusive). The analysis included all open-labeled randomized treat-to-target phase 3a trials in T1DM, where IDeg (n=223) and IGlar (n=109) were dosed once daily in a basal–bolus regimen. A1c decreased from 8.0% at baseline in both groups to 7.6 vs. 7.5% for IDeg vs. IGlar, respectively (treatment difference: 0.05 [–0.12;0.22] 95% CI). FPG decreased from 9.7 to 7.9 mmol/L for IDeg vs. 9.8 to 9.1 mmol/L for IGlar (treatment difference: –1.01 mmol/L [–1.95;–0.08] 95% CI). There was no difference in overall hypoglycemia or severe hypoglycemia. Despite the lower FPG achieved with IDeg, the rate of nocturnal hypoglycemia was lower with IDeg compared to IGlar (rate ratio: 0.68 [0.50;0.93] 95% CI). In conclusion, for patients with T1DM and baseline A1c of 7.5–8.5%, treatment with IDeg results in comparable improvement in A1c with significantly lower rate of nocturnal hypoglycemia (32%) and greater reduction in FPG compared to IGlar.