Endocrine Research Center, Institute of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, Iran University of Medical Science, No. 10, Firoozeh St., Vali-asr Ave., Vali-asr Sq, Tehran, Iran.
Department of Cardiology, Firoozgar Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
BMC Gastroenterol. 2023 Sep 23;23(1):327. doi: 10.1186/s12876-023-02948-4.
Nonalcoholic fatty liver disease (NAFLD) is a complex metabolic disorder that increases the risk for cardiovascular disease in patients with type 2 diabetes mellitus (T2DM). Global longitudinal strain (GLS) is an indicator of left ventricular (LV) mechanics and can detect subclinical myocardial dysfunction. We compared the effects of pioglitazone and empagliflozin on GLS in patients with T2DM and NAFLD without established atherosclerotic cardiovascular disease.
This study was a 24-week randomized, single-blind, and parallel-group (1: 1 ratio) clinical trial. Seventy-three participants with T2DM (being treated with metformin) and NAFLD but without established atherosclerotic cardiovascular disease (ASCVD) were randomized to empagliflozin or pioglitazone. Liver steatosis and fibrosis were measured using transient elastography, and GLS was measured by echocardiography. The primary endpoint was the change in GLS from baseline to week 24. Secondary end points include changes in controlled attenuation parameter (CAP) and Liver stiffness measure (LSM).
In this study, GLS improved by 1.56 ± 2.34% (P < 0.01) in the pioglitazone group and 1.06 ± 1.83% (P < 0.01) in the empagliflozin group without a significant difference between the two groups (P = 0.31). At baseline, GLS was inversely associated with the severity of liver fibrosis: r = - 0.311, P = 0.007. LSM in the pioglitazone and empagliflozin group [(-0.73 ± 1.59) and (-1.11 ± 1.33)] kpa (P < 0.01) decreased significantly. It was without substantial difference between the two groups (P = 0.26). Empagliflozin and pioglitazone both improved controlled attenuation parameter. The improvement was more critical in the empagliflozin group: -48.22 + 35.02 dB/m vs. -25.67 + 41.50 dB/m, P = 0.01.
Subclinical cardiac dysfunction is highly important in patients with T2DM and with NAFLD. Empagliflozin and Pioglitazone improve LV mechanics and fibrosis in patients without established ASCVD. This has a prognostic importance on cardiovascular outcomes in high-risk patients with T2DM. Moreover, empagliflozin ameliorates liver steatosis more effectively them pioglitazone. This study can serve as a start point hypothesis for the future. Further studies are needed to explore the concept in larger populations.
This trial was registered in the Iranian Registry of Clinical Trials (IRCT): "A Comparison between the Effect of Empagliflozin and Pioglitazone on Echocardiographic Indices in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease" IRCT20190122042450N5, 29 November 2020. https://www.irct.ir/search/result?query=IRCT20190122042450N5 .
非酒精性脂肪性肝病（NAFLD）是一种复杂的代谢紊乱疾病，会增加 2 型糖尿病（T2DM）患者发生心血管疾病的风险。整体纵向应变（GLS）是左心室（LV）力学的指标，可以检测亚临床心肌功能障碍。我们比较了吡格列酮和恩格列净对 T2DM 合并 NAFLD 且无明确动脉粥样硬化性心血管疾病（ASCVD）患者的 GLS 的影响。
这是一项 24 周的随机、单盲、平行分组（1:1 比例）临床试验。73 名 T2DM（正在接受二甲双胍治疗）和 NAFLD 但无明确 ASCVD 的患者被随机分为恩格列净或吡格列酮组。采用瞬时弹性成像测量肝脂肪变性和纤维化，超声心动图测量 GLS。主要终点是从基线到第 24 周 GLS 的变化。次要终点包括受控衰减参数（CAP）和肝硬度测量（LSM）的变化。
在这项研究中，吡格列酮组 GLS 改善了 1.56±2.34%（P<0.01），恩格列净组 GLS 改善了 1.06±1.83%（P<0.01），两组之间无显著差异（P=0.31）。基线时，GLS 与肝纤维化严重程度呈负相关：r=-0.311，P=0.007。吡格列酮和恩格列净组的 LSM[（-0.73±1.59）和（-1.11±1.33）kPa]（P<0.01）显著降低。两组之间无显著差异（P=0.26）。恩格列净和吡格列酮均改善了受控衰减参数。恩格列净组的改善更为显著：-48.22+35.02 dB/m 与-25.67+41.50 dB/m，P=0.01。
亚临床心脏功能障碍在 T2DM 合并 NAFLD 患者中非常重要。恩格列净和吡格列酮可改善无明确 ASCVD 患者的 LV 力学和纤维化。这对 T2DM 高危患者的心血管结局具有预后意义。此外，恩格列净在改善肝脂肪变性方面比吡格列酮更有效。本研究可以作为未来研究的起点假设。需要进一步的研究来探索更大人群中的这一概念。
这项试验在伊朗临床试验注册中心注册：“比较恩格列净和吡格列酮对 2 型糖尿病合并非酒精性脂肪性肝病患者超声心动图指标的影响”IRCT20190122042450N5，2020 年 11 月 29 日。https://www.irct.ir/search/result?query=IRCT20190122042450N5。
