Nomoto Hiroshi, Kito Kenichi, Iesaka Hiroshi, Handa Takahisa, Yanagiya Shingo, Miya Aika, Kameda Hiraku, Cho Kyu Yong, Takeuchi Jun, Nagai So, Sakuma Ichiro, Nakamura Akinobu, Atsumi Tatsuya
Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine, Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
Sapporo Diabetes and Thyroid Clinic, Sapporo, Hokkaido, Japan.
Diabetol Metab Syndr. 2023 Oct 26;15(1):214. doi: 10.1186/s13098-023-01187-7.
Pemafibrate has been reported to ameliorate lipid profiles and liver dysfunction. However, which patients derive benefit from the hepatoprotective effects of pemafibrate is unclear.
We conducted a sub-analysis of the PARM-T2D study where subjects with type 2 diabetes complicated by hypertriglyceridemia were prospectively treated with pemafibrate or conventional therapies for 52 weeks. From the original cohort, subjects who had metabolic-associated fatty liver disease without changing their treatment regimens for comorbidities were analyzed. Eligible subjects (n = 293) (average age 61.2 ± 11.7 years, 37.5% female) treated with pemafibrate (pemafibrate, n = 152) or controls who did not change their treatment regimens (controls, n = 141) were divided into three groups based on their alanine aminotransferase (ALT) levels: ALT ≤ upper normal limit (UNL) (pemafibrate, n = 65; controls, n = 50), UNL < ALT ≤ 2×UNL (pemafibrate, n = 58; controls, n = 54), and 2×UNL < ALT (pemafibrate, n = 29; controls, n = 27).
Pemafibrate treatment significantly ameliorated ALT levels (from 29 to 22 U/L, p < 0.001 by Wilcoxon's signed-rank test) in the total cohort and subjects with high ALT levels (2×ULN < ALT), and improved liver fibrosis as assessed by the Fibrosis-4 index (mean change - 0.05 (95% confidence interval: -0.22 to - 0.02), p < 0.05 versus baseline by the Mann-Whitney U-test and p < 0.05 versus the ALT ≤ UNL group by the Kruskal-Wallis test followed by Dunn's post-hoc analysis).
The hepatoprotective effects of pemafibrate were dominant in subjects with type 2 diabetes complicated with liver dysfunction.
This study was registered with the University Hospital Medical Information Network Center Clinical Trials Registry (UMIN000037385).
据报道，匹伐贝特可改善血脂谱和肝功能障碍。然而，哪些患者能从匹伐贝特的肝脏保护作用中获益尚不清楚。
我们对PARM-T2D研究进行了一项亚分析，在该研究中，2型糖尿病合并高甘油三酯血症的受试者前瞻性地接受了匹伐贝特或传统疗法治疗52周。从原始队列中，分析了患有代谢相关脂肪性肝病且未改变其合并症治疗方案的受试者。符合条件的受试者（n = 293）（平均年龄61.2±11.7岁，女性占37.5%）接受匹伐贝特治疗（匹伐贝特组，n = 152）或未改变治疗方案的对照组（对照组，n = 141），根据其丙氨酸氨基转移酶（ALT）水平分为三组：ALT≤正常上限（UNL）（匹伐贝特组，n = 65；对照组，n = 50），UNL < ALT≤2×UNL（匹伐贝特组，n = 58；对照组，n = 54），以及2×UNL < ALT（匹伐贝特组，n = 29；对照组，n = 27）。
匹伐贝特治疗显著改善了总队列以及高ALT水平（2×ULN < ALT）受试者的ALT水平（从29降至22 U/L，Wilcoxon符号秩检验p < 0.001），并通过Fibrosis-4指数评估改善了肝纤维化（平均变化-0.05（95%置信区间：-0.22至-0.02），Mann-Whitney U检验与基线相比p < 0.05，Kruskal-Wallis检验后Dunn事后分析与ALT≤UNL组相比p < 0.05）。
匹伐贝特的肝脏保护作用在2型糖尿病合并肝功能障碍的受试者中占主导地位。
本研究已在大学医院医学信息网络中心临床试验注册中心（UMIN000037385）注册。
