Clinical perspectives from the BEGIN and EDITION programmes: Trial-level meta-analyses outcomes with either degludec or glargine 300 U/mL vs glargine 100 U/mL in T2DM - 15/03/18

Doi : 10.1016/j.diabet.2018.02.002

R. Roussel ^a,^b,^c,^⁎ , R. Ritzel ^d, E. Boëlle-Le Corfec ^e, B. Balkau ^f,^g,^h, J. Rosenstock ⁱ
^a Inserm U1138, Centre de recherche des Cordeliers, 75006 Paris, France
^b Université Paris Diderot, Sorbonne Paris Cité, 75013 Paris, France
^c Département de diabétologie, endocrinologie et nutrition, DHU FIRE, hôpital Bichat, AP–HP, 75018 Paris, France
^d Division of Endocrinology and Diabetes, Klinikum Schwabing and Klinikum Bogenhausen, Städtisches Klinikum München GmbH, 81925 Munich, Germany
^e Sanofi, 75008 Paris, France
^f CESP, faculty of medicine, university Paris-South, 94807 Villejuif, France
^g Faculty of Medicine, University Versailles-St-Quentin, 78000 Versailles, France
^h Inserm U1018, University Paris-Saclay, 94807 Villejuif, France
ⁱ Dallas Diabetes Research Center at Medical City, Dallas, 75230 TX, USA

^⁎Corresponding author. Département de diabétologie, endocrinologie et nutrition, DHU FIRE, hôpital Bichat, Assistance publique Hôpitaux de Paris, 46, rue Henri-Huchard, Paris 75018, France.

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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 HbA_1c, 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, HbA_1c reduction was greater with Gla-100 (mean difference [95% CI] in HbA_1c change: 0.09 [0.01–0.18] %) whereas in EDITION, there was no difference in FPG and HbA_1c 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 HbA_1c versus Gla-100, with a hypoglycaemia benefit only evident at night. In contrast, Gla-300 showed similar HbA_1c 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.

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Keywords : Insulin degludec, Insulin glargine 300U/mL, Phase-3 clinical trials, Trial-level meta-analyses, Type-2 diabetes mellitus