Pai Vikas, Paneerselvam A, Mukhopadhyay Satinath, Bhansali Anil, Kamath Dinesh, Shankar V, Gambhire Dhiraj, Jani Rajendrakumar H, Joshi Shashank, Patel Pankaj
Pai Clinic & Diagnostic Centre, Pune, India.
Aruna Diabetes Centre, Chennai, India.
J Diabetes Sci Technol. 2014 Jan;8(1):132-141. doi: 10.1177/1932296813518680. Epub 2014 Jan 16.
Dual PPARα/γ can improve both metabolic effects and minimized the side effects caused by either PPARα or PPARγ agonist. The PRESS V study was aimed to evaluate the safety, tolerability, and efficacy of saroglitazar 2 mg and 4 mg capsules (Lipaglyn™; Zydus Code: ZYH1) as compared to high dose pioglitazone in patients with diabetic dyslipidemia. In this 26-week double-blind, parallel arm, phase 3 study patients with hypertriglyceridemia with type 2 diabetes mellitus (BMI > 23 kg/m; hypertriglyceridemia: TG > 200 to 400 mg/dL; glycosylated hemoglobin [HbA] >7 to 9%) were enrolled from 14 sites in India. After 2 weeks of lifestyle modification, 122 patients were randomized double-blind to 24-week treatment with the study drugs (saroglitazar 2 mg or 4 mg or pioglitazone 45 mg once daily) in a 1:1:1 ratio. The primary end point was change in plasma triglyceride level at week 24. The secondary end points were change in lipid profile and fasting plasma glucose at week 24. Patients who received study medication and had undergone at least 1 postbaseline efficacy evaluation were included in the efficacy analysis. All randomized patients who received at least a single dose were included for safety evaluation. The efficacy analysis included 109 patients (n = 37 in saroglitazar 2 mg; n = 39 in saroglitazar 4 mg; n = 33 in pioglitazone). Saroglitazar 2 mg and 4 mg significantly reduced (P < .001) plasma triglyceride from baseline by 26.4% (absolute change ± SD: -78.2 ± 81.98 mg/dL) and 45% (absolute change ± SD -115.4 ± 68.11 mg/dL), respectively, as compared to pioglitazone -15.5% (absolute change ± SD: -33.3 ± 162.41 mg/dL) at week 24. Saroglitazar 4 mg treatment also demonstrated marked decrease in low-density lipoprotein (5%), very-low-density lipoprotein (45.5%), total cholesterol (7.7%), and apolipoprotein-B (10.9%). Saroglitazar treatment was generally safe and well tolerated. No serious adverse events were reported in saroglitazar treatment arm and no persistent change in laboratory parameters. Saroglitazar appeared to be an effective and safe therapeutic option for improving hypertriglyceridemia in patients with type 2 diabetes mellitus.
双重PPARα/γ激动剂既能改善代谢效应，又能将PPARα或PPARγ激动剂所引起的副作用降至最低。PRESS V研究旨在评估2毫克和4毫克沙格列他唑胶囊（Lipaglyn™；Zydus代码：ZYH1）与高剂量吡格列酮相比，在糖尿病血脂异常患者中的安全性、耐受性和疗效。在这项为期26周的双盲、平行组、3期研究中，来自印度14个地点的2型糖尿病伴高甘油三酯血症患者（BMI>23 kg/m²；高甘油三酯血症：TG>200至400 mg/dL；糖化血红蛋白[HbA₁c]>7%至9%）被纳入研究。在进行2周的生活方式调整后，122名患者以1:1:1的比例随机双盲接受研究药物（沙格列他唑2毫克或4毫克或吡格列酮45毫克，每日一次）治疗24周。主要终点是第24周时血浆甘油三酯水平的变化。次要终点是第24周时血脂谱和空腹血糖的变化。接受研究药物治疗且至少进行过1次基线后疗效评估的患者被纳入疗效分析。所有接受至少单剂量治疗的随机分组患者被纳入安全性评估。疗效分析包括109名患者（沙格列他唑2毫克组n = 37；沙格列他唑4毫克组n = 39；吡格列酮组n = 33）。与第24周时吡格列酮降低15.5%（绝对变化±标准差：-33.3±162.41 mg/dL）相比，沙格列他唑2毫克和4毫克组分别使血浆甘油三酯从基线水平显著降低（P <.001）26.4%（绝对变化±标准差：-78.2±81.98 mg/dL）和45%（绝对变化±标准差-115.4±68.11 mg/dL）。沙格列他唑4毫克治疗还使低密度脂蛋白（降低5%）、极低密度脂蛋白（降低45.5%）、总胆固醇（降低7.7%）和载脂蛋白B（降低10.9%）显著下降。沙格列他唑治疗总体安全且耐受性良好。沙格列他唑治疗组未报告严重不良事件，实验室参数也无持续变化。沙格列他唑似乎是改善2型糖尿病患者高甘油三酯血症的一种有效且安全的治疗选择。
