Aims: To explore comparative glycaemic control and hypoglycaemia incidence with insulin degludec 100U/mL (IDeg) or insulin glargine 300U/mL (Gla-300) versus glargine 100U/mL (Gla-100) in trial-level meta-analyses of phase 3a clinical trials including people with type-2 diabetes.
Methods: Meta-analyses of HbA1c, fasting plasma glucose (FPG), average 24h self-measured plasma glucose (SMPG), pre-breakfast SMPG and hypoglycaemia incidence and rate, using data from the BEGIN (IDeg) and EDITION (Gla-300) insulin development programmes, were performed.
Results: In BEGIN, despite greater FPG reduction with IDeg than Gla-100, HbA1c reduction was greater with Gla-100 (mean difference [95% CI] in HbA1c change: 0.09 [0.01-0.18] %) whereas in EDITION, there was no difference in FPG and HbA1c reduction between Gla-300 and Gla-100. Risk of nocturnal confirmed (<3.1mmol/L [<56mg/dL]) or severe hypoglycaemia, but not anytime (24h) events, was lower with IDeg than Gla-100 (relative risk [RR] 0.79 [0.66-0.94]) whereas Gla-300 was associated with reduced risk of nocturnal (RR 0.75 [0.61-0.92]) and anytime (24h) (RR 0.81 [0.69-0.94]) confirmed (<3.0mmol/L [<54mg/dL]) or severe hypoglycaemia versus Gla-100.
Conclusions: These trial-level meta-analyses suggest that despite greater reductions in FPG, IDeg was associated with less improvement in HbA1c versus Gla-100, with a hypoglycaemia benefit only evident at night. In contrast, Gla-300 showed similar HbA1c reduction to Gla-100, accompanied by lower risk of hypoglycaemia both at night and at any time of day. Gla-300 and IDeg appear more similar than dissimilar, but head-to-head trials are required.
Keywords: Insulin degludec; Insulin glargine 300U/mL; Phase-3 clinical trials; Trial-level meta-analyses; Type-2 diabetes mellitus.
Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.