Indirect comparison of lixisenatide versus neutral protamine Hagedorn insulin as add-on to metformin and sulphonylurea in patients with type 2 diabetes mellitusLixisenatid versus NPH-Insulin als Therapieintensivierung nach Metformin und Sulfonylharnstoff bei Patienten mit Typ 2 Diabetes mellitus – Ergebnisse eines indirekten Vergleichs

GMS German Medical Science — an Interdisciplinary Journal

Walter Lehmacher³  Gerhard H. Scholz⁴  Karlheinz Theobald¹  Maeva Germe²  Marie Fournier² 

[1] Sanofi, Frankfurt, Germany;Sanofi, Paris, France;Institute for Medical Statistics, Informatics and Epidemiology, University of Cologne, Germany;St. ElisabethKrankenhaus, Department of Endocrinology, Diabetology, Cardiology and General Medicine, Leipzig, Germany

关键词: adjusted indirect comparison;    type 2 diabetes;    weight change;    hypoglycaemia;    basal insulin;    lixisenatide;   

Others  :  1075760

实施日期：2013-08-22，发布日期：2014-10-16

【 摘 要 】

Objective: There is currently a lack of evidence from direct comparisons of treatment outcomes with lixisenatide versus neutral protamine Hagedorn (NPH)-insulin in type 2 diabetes mellitus (T2DM) patients with suboptimal glycaemic control with oral antidiabetic drugs (OADs). Hence, the current analysis indirectly compared available evidence on the risk of hypoglycaemia and weight change between lixisenatide and NPH-insulin based on randomized controlled trial (RCT) data with exenatide, insulin glargine and placebo as common references.

Methods: A systematic search of PubMed, Embase, the Cochrane database and clinical registries identified English- and German-language articles published from January 1980 to October 2012 reporting data from RCTs. Only publications of trials that reported outcomes from 24 to 30 weeks comparing glucagon-like peptide-1 receptor agonists or basal insulin versus another antidiabetic agent or placebo were included. Hypoglycaemia, patients at glycated haemoglobin (HbA_1c) target and discontinuations due to adverse events (AEs) were treated as binary variables, with risk ratios and odds ratios (ORs) calculated. HbA_1c and body weight were treated as continuous variables with difference in mean change from baseline (MD) calculated. Meta-analyses were performed with random effects models and indirect comparisons were performed according to Bucher’s method.

Results: Seven RCTs (n=3,301 patients) comparing the efficacy and safety of lixisenatide, exenatide, insulin glargine and NPH-insulin with different antidiabetic treatments in adult patients with T2DM were included in the final analysis. In the adjusted indirect comparison, there was a significant difference in symptomatic hypoglycaemia (OR = 0.38; 95% CI = [0.17, 0.85]) and in confirmed hypoglycaemia (OR = 0.46; 95% CI = [0.22, 0.96]) favouring lixisenatide over NPH-insulin and comparable changes in HbA_1c from baseline (MD = 0.07%; 95% CI = [–0.26%, 0.41%]). In contrast to NPH-insulin, there was a significant reduction in body weight with lixisenatide (MD = –3.62 kg; 95% CI = [–5.86 kg, –1.38 kg]) at study completion. The number of discontinuations due to AEs numerically favoured NPH-insulin over lixisenatide (OR = 2.64; 95% CI = [0.25, 27.96]), with a broad confidence interval.

Conclusions: Lixisenatide treatment was associated with a lower risk of hypoglycaemia and a greater weight loss compared with NPH-insulin. Glycaemic control with lixisenatide treatment was comparable with NPH-insulin. These data suggest that lixisenatide is a beneficial treatment option for T2DM patients with inadequate glycaemic control on OADs, and is associated with reduced risk of hypoglycaemia and weight gain.

【 授权许可】

   
© 2014 Fournier et al.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

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• [39]Appendix 1: Selection criteria used to assess studies for the oral antidiabetic drug and basal insulin systematic reviews(000199_Attachment1.pdf, application/pdf,71,92 kByte)
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• [41]Appendix 3: Sensitivity analyses: indirect comparison of lixisenatide vs. NPH without consideration of the studies investigating exenatide or calculating the indirect comparison via insulin glargine as a reference(000199_Attachment3.pdf, application/pdf,90,09 kByte)
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