Safety, efficacy, and cost-effectiveness of insulin degludec U100 versus insulin glargine U300 in adults with type 1 diabetes: a systematic review and indirect treatment comparison

Background: Clinical differences between degludec U100 (Deg-100) and glargine U300 (Gla-300) in type 1 diabetes (T1D) were unknown. Aim: To indirectly compare the safety, efficacy, and cost-effectiveness between Deg-100 and Gla-300 in T1D adults via systematic review. Method: Medline, the Cochrane Library, ClinicalTrials.gov, and Google Scholar were searched (October 2021). Randomized controlled trials comparing Deg-100 or Gla-300 vs. glargine U100 in T1D adults (follow-up ≥ 12 weeks) were selected and analyzed using a frequentist network meta-analysis. Cost-effectiveness analysis (CEA) was conducted over a 1-year time horizon from societal perspectives. Results: Nine trials were included. Efficacy analysis suggested that Deg-100 was non-inferior to Gla-300 in reducing HbA1c (MD 0.03 [95% CI − 0.09 to 0.15]; P = 0.60), FPG (MD − 1.12 [− 2.19 to − 0.04]; P = 0.04), and pre-breakfast SMBG (MD − 0.71 [− 1.46 to 0.03]; P = 0.06). Safety analysis suggested that Deg-100 appeared to have lower rates of both severe (HR 0.44 [0.25–0.78]; P = 0.005) and nocturnal severe (HR 0.19 [0.08–0.44]; P < 0.001) hypoglycemia, with lower total (MD − 0.07 [− 0.13 to − 0.01]; P = 0.02) and basal (MD − 0.08 [− 0.12 to − 0.04]; P < 0.001) insulin doses compared with Gla-300. No significant differences were observed for other hypoglycemia outcomes, adverse events, serious adverse events, bolus insulin dose, and body weight. The CEA showed that Deg-100 appeared to be a dominant treatment in Japan (+ 0.0283 QALYs, ¥26,266 [$228] per patient) and the United States (+ 0.0267 QALYs, $986 per patient). Conclusion: Low-certainty indirect evidence suggested that Deg-100 appeared to have a favorable reduction in rates of severe hypoglycemia and more cost-effective compared with Gla-300 in T1D adults.