Effects of luseogliflozin on suspected MASLD in patients with diabetes: a pooled meta-analysis of phase III clinical trials

Author:

Kawaguchi TakumiORCID,Murotani Kenta,Kajiyama Hiromitsu,Obara Hitoshi,Yamaguchi Hironori,Toyofuku Yuko,Kaneko Fumi,Seino Yutaka,Uchida Saeko

Abstract

Abstract Background Luseogliflozin, a sodium–glucose cotransporter 2 inhibitor, potentially exerts pleiotropic effects on the liver. However, the sufficient evidence is still lacking. We aimed to investigate the effects of luseogliflozin on hepatic steatosis, fibrosis, and cardiometabolic risk factors in diabetic patients by a pooled meta-analysis. Methods In this pooled meta-analysis, we enrolled diabetic patients who participated in phase III clinical trials of luseogliflozin (luseogliflozin group n = 302, placebo group n = 191). The primary outcomes were changes in fatty liver index (FLI) and Hepamet fibrosis score (HFS) after 24 weeks. The secondary outcomes were changes in cardiometabolic risk factors after 24 weeks. Statistical analysis was performed using propensity scoring analysis by the inverse probability of treatment weighting method. Results Primary outcomes: Luseogliflozin significantly decreased FLI compared to placebo after 24 weeks (adjusted coefficient − 5.423, 95%CI − 8.760 to − 2.086, P = 0.0016). There was no significant difference in changes in HFS between the two groups. However, luseogliflozin significantly decreased HFS compared to placebo in diabetic patients with ALT > 30 U/L (adjusted coefficient − 0.039, 95%CI − 0.077 to − 0.001, P = 0.0438) and with FIB-4 index > 1.3 (adjusted coefficient − 0.0453, 95%CI − 0.075 to − 0.016, P = 0.0026). Secondary outcom8es: Luseogliflozin significantly decreased HbA1c level, HOMA-IR value, BMI, and uric acids level, and increased HDL cholesterol level compared to placebo. Conclusions This pooled meta-analysis demonstrated that 24-week treatment with luseogliflozin improved hepatic steatosis and fibrosis indexes in diabetic patients, especially those with liver injury. Furthermore, luseogliflozin improved various cardiometabolic risk factors. Thus, luseogliflozin may be useful for improving MASLD in diabetic patients. Graphical abstract

Funder

Taisho Pharmaceutical Co., Ltd.

Publisher

Springer Science and Business Media LLC

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