Objective Type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease (diabetic MASLD) frequently coexist and worsen liver and non-liver outcomes, but effective pharmacological therapies are limited. We aimed to evaluate the long-term effect of sodium-glucose cotransporter-2 inhibitor (SGLT-2i) on liver and non-liver outcomes among patients with diabetic MASLD. Design This population-based cohort study retrieved patients with diabetic MASLD from Merative Marketscan Research Databases (April 2013 and December 2021). The active comparator was other glucose-lowering drugs (oGLDs). Primary outcomes were liver complications including hepatocellular carcinoma (HCC) and liver cirrhosis, as well as non-liver complications including cardiovascular disease (CVD), chronic kidney disease (CKD) and non-liver cancer. Propensity score matching was applied and Cox regression models were conducted. Results Compared with oGLD, SGLT-2i users had significantly lower risk of HCC (HR 0.76, 95% CI 0.62 to 0.93), liver cirrhosis (HR 0.80, 95% CI 0.76 to 0.84), CVD (HR 0.82, 95% CI 0.79 to 0.85) and CKD (HR 0.66, 95% CI 0.62 to 0.70), non-liver cancer (HR 0.81, 95% CI 0.76 to 0.86). Compared with patients without metformin and SGLT-2i, a stepwise decreasing risk was observed in users of either metformin or SGLT-2i (HRs 0.76–0.97) and in users of both medications (HRs 0.58–0.79). The lower risk also was shown in liver decompensation, compensated cirrhosis, major CVD, end-stage renal disease and specific common cancers (HRs 0.61–0.84). Conclusion In a nationwide cohort, SGLT-2i users were associated with a substantially lower risk of liver and non-liver complications than oGLD users among patients with diabetic MASLD. The risk was further reduced with concomitant metformin use. Data may be obtained from a third party and are not publicly available.

中文翻译：

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钠-葡萄糖协同转运蛋白-2 抑制剂和二甲双胍对 2 型糖尿病和代谢功能障碍相关脂肪性肝病患者肝脏和非肝脏并发症的协同作用


目的 2 型糖尿病和代谢功能障碍相关脂肪性肝病 （diabetic MASLD） 经常共存并恶化肝脏和非肝脏结局，但有效的药物治疗有限。我们旨在评估钠-葡萄糖协同转运蛋白 2 抑制剂 （SGLT-2i） 对糖尿病 MASLD 患者肝脏和非肝脏结局的长期影响。设计 这项基于人群的队列研究从 Merative Marketscan 研究数据库（2013 年 4 月和 2021 年 12 月）检索了糖尿病 MASLD 患者。活性对照是其他降糖药物 （oGLDs）。主要结局是肝脏并发症，包括肝细胞癌 （HCC） 和肝硬化，以及非肝脏并发症，包括心血管疾病 （CVD） 、慢性肾脏病 （CKD） 和非肝癌。应用倾向得分匹配并进行 Cox 回归模型。结果 与 oGLD 相比，SGLT-2i 使用者患 HCC （HR 0.76， 95% CI 0.62 至 0.93）、肝硬化 （HR 0.80， 95% CI 0.76 至 0.84）、CVD （HR 0.82， 95% CI 0.79 至 0.85） 和 CKD （HR 0.66， 95% CI 0.62 至 0.70）、非肝癌 （HR 0.81， 95% CI 0.76 至 0.86） 的风险显著降低。与没有二甲双胍和 SGLT-2i 的患者相比，在二甲双胍或 SGLT-2i 使用者 （HRs 0.76-0.97） 和两种药物的使用者 （HRs 0.58-0.79） 中观察到风险逐步降低。肝功能失代偿、代偿期肝硬化、主要 CVD、终末期肾病和特定常见癌症 （HRs 0.61-0.84） 也显示出较低的风险。结论 在全国队列中，在糖尿病 MASLD 患者中，SGLT-2i 使用者的肝脏和非肝脏并发症风险显著低于 oGLD 使用者。 同时使用二甲双胍进一步降低了风险。数据可能从第三方获得，并且不会公开。