Virginia Commonwealth University, Richmond, Virginia.
Zydus Therapeutics Inc USA, Pennington, NJ.
Clin Gastroenterol Hepatol. 2023 Sep;21(10):2597-2605.e2. doi: 10.1016/j.cgh.2023.01.018. Epub 2023 Jan 31.
BACKGROUND & AIMS: Cardiovascular disease is the leading cause of mortality in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the effects of saroglitazar, a dual peroxisome proliferator-activated receptor α/γ agonist, on serum lipids in patients with NAFLD.
A total of 221 patients (saroglitazar, 130; placebo, 91) with NAFLD from phase 2 and 3 double-blinded placebo-controlled randomized clinical trials were pooled to assess the impact of saroglitazar magnesium 4 mg on traditional lipids, very low density lipoprotein cholesterol (VLDL-C), and small dense LDL-C (sdLDL-C). Change from baseline in lipid parameters was performed by using analysis of covariance including treatment as fixed effect and baseline value, diabetes, hypertension, and statin use as covariates.
Treatment with saroglitazar significantly improved total cholesterol (-17 mg/dL, 95% confidence interval [CI], -24 to 9; P < .001), triglyceride (-45 mg/dL, 95% CI, -60 to 31; P < .001), low-density lipoprotein cholesterol (-8 mg/dL, 95% CI, -15 to -1; P = .01), and VLDL-C (-8 mg/dL, -14 to -3; P < .001). Saroglitazar improved serum lipids as early as 4-6 weeks of initiation of therapy, and these effects persisted for duration of therapy. Saroglitazar also improved the highly atherogenic sdLDL-C (-10 mg/dL, -17 to -2; P = .01). In subgroup analysis of patients with either diabetes or hypertension, saroglitazar significantly improved serum lipids.
Saroglitazar improved the serum atherogenic lipoprotein profile in patients with NAFLD, irrespective of comorbid conditions and statin use. Saroglitazar has the potential to not only positively affect liver disease but also reduce cardiovascular risk in patients with NAFLD. (Trials registrations: CTRI 2015/10/006236, CTRI 173300410A0106, NCT03863574, and NCT03061721).
心血管疾病是导致非酒精性脂肪性肝病（NAFLD）患者死亡的主要原因。本研究旨在评估过氧化物酶体增殖物激活受体α/γ双重激动剂沙格列汀对 NAFLD 患者血清脂质的影响。
共纳入来自 2 项 2 期和 3 期双盲安慰剂对照随机临床试验的 221 例 NAFLD 患者（沙格列汀组 130 例，安慰剂组 91 例），评估沙格列汀镁 4mg 对传统脂质、极低密度脂蛋白胆固醇（VLDL-C）和小而密低密度脂蛋白胆固醇（sdLDL-C）的影响。采用协方差分析比较基线时的脂质参数变化，其中治疗为固定效应，基线值、糖尿病、高血压和他汀类药物的使用为协变量。
与安慰剂相比，沙格列汀治疗可显著改善总胆固醇（-17mg/dL，95%置信区间[CI]，-24 至 9；P<0.001）、甘油三酯（-45mg/dL，95%CI，-60 至 31；P<0.001）、低密度脂蛋白胆固醇（-8mg/dL，95%CI，-15 至 -1；P=0.01）和 VLDL-C（-8mg/dL，-14 至 -3；P<0.001）。沙格列汀治疗后 4-6 周即可改善血脂，且治疗期间持续改善。沙格列汀还可改善致动脉粥样硬化的 sdLDL-C（-10mg/dL，-17 至 -2；P=0.01）。在伴有糖尿病或高血压的患者亚组分析中，沙格列汀可显著改善血脂。
沙格列汀可改善 NAFLD 患者的血清致动脉粥样硬化脂蛋白谱，无论合并症和他汀类药物的使用情况如何。沙格列汀不仅有改善肝脏疾病的潜力，还有降低 NAFLD 患者心血管风险的潜力。（临床试验注册号：CTRI 2015/10/006236、CTRI 173300410A0106、NCT03863574 和 NCT03061721）。
