Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
Endocrine Unit, Department of Medicine, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
Dig Dis Sci. 2020 Feb;65(2):623-631. doi: 10.1007/s10620-019-5477-1. Epub 2019 Jan 25.
Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a novel class of drugs that lower glucose by inducing renal glycosuria. We aimed to explore whether SGLT2 inhibitor added to the usual care for patients with type 2 diabetes mellitus (T2DM) and biopsy-proven nonalcoholic steatohepatitis (NASH) will benefit NASH histology.
In this investigator-initiated, single-arm, open-label, pilot study, nine biopsy-proven NASH patients with T2DM were given empagliflozin 25 mg daily for 24 weeks. Liver biopsy was repeated at the end of treatment. The histological outcomes were compared with the placebo group of a previous 48-week clinical trial.
There was a significant reduction in body mass index (median change, Δ = -0.7 kg per m, p = 0.011), waist circumference (Δ = -3 cm, p = 0.033), systolic blood pressure (Δ = -9 mmHg, p = 0.024), diastolic blood pressure (Δ = -6 mmHg, p = 0.033), fasting blood glucose (Δ = -1.7 mmol/L, p = 0.008), total cholesterol (Δ = -0.5 mmol/L, p = 0.011), gamma glutamyl transpeptidase (Δ = -19 U/L, p = 0.013), volumetric liver fat fraction (Δ = -7.8%, p = 0.017), steatosis (Δ = -1, p = 0.014), ballooning (Δ = -1, p = 0.034), and fibrosis (Δ = 0, p = 0.046). All histological components either remained unchanged or improved, except in one patient who had worsening ballooning. Empagliflozin resulted in significantly greater improvements in steatosis (67% vs. 26%, p = 0.025), ballooning (78% vs. 34%, p = 0.024), and fibrosis (44% vs. 6%, p = 0.008) compared with historical placebo.
This pilot study provides primary histological evidence that empagliflozin may be useful for the treatment of NASH. This preliminary finding should prompt larger clinical trials to assess the effectiveness of empagliflozin and other SGLT2 inhibitors for the treatment of NASH in T2DM patients. Trial registry number ClincialTrials.gov number, NCT02964715.
钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂是一类新型药物，通过诱导肾性糖尿来降低血糖。我们旨在探讨 SGLT2 抑制剂是否会有益于伴有非酒精性脂肪性肝炎（NASH）的 2 型糖尿病（T2DM）患者的 NASH 组织学。
在这项由研究者发起的、单臂、开放标签、试点研究中，9 名活检证实的 NASH 合并 T2DM 患者每天给予恩格列净 25mg，治疗 24 周。治疗结束时再次进行肝活检。将组织学结果与之前的 48 周临床试验的安慰剂组进行比较。
体重指数（中位数变化，Δ=−0.7kg/m，p=0.011）、腰围（Δ=−3cm，p=0.033）、收缩压（Δ=−9mmHg，p=0.024）、舒张压（Δ=−6mmHg，p=0.033）、空腹血糖（Δ=−1.7mmol/L，p=0.008）、总胆固醇（Δ=−0.5mmol/L，p=0.011）、γ-谷氨酰转肽酶（Δ=−19U/L，p=0.013）、肝脂肪容积分数（Δ=−7.8%，p=0.017）、肝脂肪变性（Δ=−1，p=0.014）、气球样变（Δ=−1，p=0.034）和纤维化（Δ=0，p=0.046）均显著降低。除 1 例患者气球样变加重外，所有组织学指标均保持不变或改善。恩格列净治疗后，肝脂肪变性（67% vs. 26%，p=0.025）、气球样变（78% vs. 34%，p=0.024）和纤维化（44% vs. 6%，p=0.008）的改善明显优于历史安慰剂。
这项初步研究提供了原发性组织学证据，表明恩格列净可能对 NASH 的治疗有用。这一初步发现应促使更大规模的临床试验来评估恩格列净和其他 SGLT2 抑制剂治疗 T2DM 患者 NASH 的疗效。临床试验注册号：ClincialTrials.gov 注册号，NCT02964715。
