Department of Medicine, Division of Endocrinology, University of California San Diego, San Diego, CA, USA.
Gilead Pharmaceuticals, Foster City, CA, USA.
Diabetes Obes Metab. 2016 May;18(5):463-74. doi: 10.1111/dom.12629. Epub 2016 Feb 23.
To report the results of two phase III trials assessing the efficacy of ranolazine for glycaemic control in patients with type 2 diabetes on metformin or glimepiride background therapy.
In two double-blind trials we randomized 431 and 442 patients with type 2 diabetes to ranolazine 1000 mg twice daily versus placebo added to either glimepiride (glimepiride add-on study) or metformin background therapy (metformin add-on study). Patients receiving ranolazine added to metformin had their metformin dose halved (with the addition of a metformin-matched placebo) relative to the placebo group to correct for a metformin-ranolazine pharmacokinetic interaction. The primary endpoint of the trials was the change from baseline in glycated haemoglobin (HbA1c) at week 24.
When added to glimepiride, ranolazine caused a 0.51% least squares mean [95% confidence interval (CI) 0.71, 0.32] decrease from baseline in HbA1c at 24 weeks relative to placebo and roughly doubled the proportion of patients achieving an HbA1c of <7% (27.1 vs 14.1%; p = 0.001). When added to metformin background therapy, there was no significant difference in the 24-week HbA1c change from baseline [placebo-corrected LS mean difference -0.11% (95% CI -0.31, 0.1)].
Compared with placebo, addition of ranolazine in patients with type 2 diabetes treated with glimepiride, but not metformin, significantly reduced HbA1c over 24 weeks. The decreased dose of metformin used in the metformin add-on study complicates the interpretation of this trial. Whether an effective regimen of ranolazine added to metformin for glycaemic control can be identified remains unclear.
报告两项评估雷诺嗪在二甲双胍或格列美脲背景治疗的 2 型糖尿病患者血糖控制疗效的 III 期临床试验结果。
在两项双盲试验中，我们将 431 例和 442 例 2 型糖尿病患者随机分为瑞那嗪 1000mg 每日两次与安慰剂分别添加至格列美脲（格列美脲添加研究）或二甲双胍背景治疗（二甲双胍添加研究）。接受瑞那嗪添加二甲双胍的患者将其二甲双胍剂量减半（添加二甲双胍匹配安慰剂），以纠正二甲双胍-瑞那嗪药代动力学相互作用。试验的主要终点为 24 周时从基线糖化血红蛋白（HbA1c）的变化。
当添加至格列美脲时，与安慰剂相比，瑞那嗪在 24 周时使 HbA1c 从基线降低了 0.51%（95%置信区间[CI]：0.71，0.32），并且大约使达到 HbA1c<7%的患者比例增加了一倍（27.1%比 14.1%；p=0.001）。当添加至二甲双胍背景治疗时，与基线相比，24 周 HbA1c 变化无显著差异[安慰剂校正 LS 均值差值-0.11%（95%CI：-0.31，0.1）]。
与安慰剂相比，在接受格列美脲治疗的 2 型糖尿病患者中添加瑞那嗪可显著降低 24 周时的 HbA1c。在二甲双胍添加研究中使用的减少剂量的二甲双胍使该试验的解释复杂化。是否可以确定添加瑞那嗪用于血糖控制的有效方案仍不清楚。
