R Roussel1, R Ritzel2, E Boëlle-Le Corfec3, B Balkau4, J Rosenstock5. 1. Inserm U1138, Centre de recherche des Cordeliers, 75006 Paris, France; Université Paris Diderot, Sorbonne Paris Cité, 75013 Paris, France; Département de diabétologie, endocrinologie et nutrition, DHU FIRE, hôpital Bichat, AP-HP, 75018 Paris, France. Electronic address: ronan.roussel@gmail.com. 2. Division of Endocrinology and Diabetes, Klinikum Schwabing and Klinikum Bogenhausen, Städtisches Klinikum München GmbH, 81925 Munich, Germany. 3. Sanofi, 75008 Paris, France. 4. CESP, faculty of medicine, university Paris-South, 94807 Villejuif, France; Faculty of Medicine, University Versailles-St-Quentin, 78000 Versailles, France; Inserm U1018, University Paris-Saclay, 94807 Villejuif, France. 5. Dallas Diabetes Research Center at Medical City, Dallas, 75230 TX, USA.
Abstract
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.
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.
Authors: Philip D Home; Richard M Bergenstal; Geremia B Bolli; Monika Ziemen; Maria Rojeski; Melanie Espinasse; Matthew C Riddle Journal: Diabetes Obes Metab Date: 2017-08-08 Impact factor: 6.577
Authors: Sean D Sullivan; Charlie J Nicholls; Rishab A Gupta; Arjun A Menon; Jasmanda Wu; Jukka Westerbacka; Zsolt Bosnyak; Juan P Frias; Timothy S Bailey Journal: Diabetes Obes Metab Date: 2019-06-21 Impact factor: 6.577