Fournier Marie, Germe Maeva, Theobald Karlheinz, Scholz Gerhard H, Lehmacher Walter
Sanofi, Paris, France.
Sanofi, Frankfurt, Germany.
Ger Med Sci. 2014 Oct 16;12:Doc14. doi: 10.3205/000199. eCollection 2014.
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.
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 (HbA1c) target and discontinuations due to adverse events (AEs) were treated as binary variables, with risk ratios and odds ratios (ORs) calculated. HbA1c 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.
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 HbA1c 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.
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.
目前，在口服抗糖尿病药物（OAD）治疗后血糖控制不佳的2型糖尿病（T2DM）患者中，缺乏利司那肽与中性鱼精蛋白锌胰岛素（NPH）治疗效果直接对比的证据。因此，本分析基于随机对照试验（RCT）数据，以艾塞那肽、甘精胰岛素和安慰剂作为共同对照，间接比较了利司那肽与NPH胰岛素之间低血糖风险和体重变化的现有证据。
通过对PubMed、Embase、Cochrane数据库和临床注册库进行系统检索，确定了1980年1月至2012年10月发表的报告RCT数据的英文和德文文章。仅纳入了报告24至30周结果的试验出版物，这些试验比较了胰高血糖素样肽-1受体激动剂或基础胰岛素与另一种抗糖尿病药物或安慰剂。低血糖、糖化血红蛋白（HbA1c）达标患者以及因不良事件（AE）停药的情况被视为二元变量，计算风险比和比值比（OR）。HbA1c和体重被视为连续变量，计算基线平均变化差异（MD）。采用随机效应模型进行荟萃分析，并根据Bucher方法进行间接比较。
最终分析纳入了7项RCT（n = 3301例患者），比较了利司那肽、艾塞那肽、甘精胰岛素和NPH胰岛素与不同抗糖尿病治疗方案在成年T2DM患者中的疗效和安全性。在调整后的间接比较中，症状性低血糖（OR = 0.38；95%CI = [0.17, 0.85]）和确诊低血糖（OR = 0.46；95%CI = [0.22, 0.96]）方面存在显著差异，利司那肽优于NPH胰岛素，且HbA1c从基线的变化相当（MD = 0.07%；95%CI = [-0.26%, 0.41%]）。与NPH胰岛素相反，在研究结束时，利司那肽使体重显著降低（MD = -3.62 kg；95%CI = [-5.86 kg, -1.38 kg]）。因AE停药的数量在数值上NPH胰岛素比利司那肽更有利（OR = 2.64；95%CI = [0.25, 27.96]），置信区间较宽。
与NPH胰岛素相比，利司那肽治疗低血糖风险较低，体重减轻更多。利司那肽治疗血糖控制与NPH胰岛素相当。这些数据表明，利司那肽对于OAD治疗血糖控制不佳的T2DM患者是一种有益的治疗选择，且与低血糖和体重增加风险降低相关。
