LMC Diabetes and Endocrinology Brampton, 2979, Bovaird Dr. E, L6S0C6 Brampton, Ontario, Canada; Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, 60, Murray street, M5T3L9 Toronto, Ontario, Canada.
LMC Diabetes and Endocrinology Toronto, 1929, Bayview avenue, M4G3E8 Toronto, Ontario, Canada.
Diabetes Metab. 2018 Dec;44(6):493-499. doi: 10.1016/j.diabet.2018.08.001. Epub 2018 Aug 24.
The impact of new classes of glucose lowering medications on markers of non-alcoholic fatty liver disease (NAFLD) associated with type 2 diabetes (T2D) have been inconsistent in their magnitude and independence. This large retrospective study investigates changes in alanine aminotransferase (ALT) levels among subjects initiated on newer classes of T2D medications in comparison to a reference control group.
We studied people with T2D from a large Canadian diabetes register, who had canagliflozin, dapagliflozin, liraglutide, sitagliptin or no further treatment added to their diabetes treatments. Stepwise multiple regression was used to determine the association of A1c and weight change on ALT. Propensity score weighting was used to balance baseline characteristics between treatment groups.
A total of 3667 subjects met study criteria. ALT levels (mean follow-up 4.8 months) were lower after treatment with sodium glucose co-transporter 2 (SGLT2) inhibitors, canagliflozin (-4.3U/L, P<0.01) and dapagliflozin (-3.5U/L, P<0.01), compared to incretin agents, liraglutide (-2.1U/L, P<0.01) and sitagliptin (-1.8U/L, P<0.01), each greater than the control group. Only the SGLT2 inhibitor treatment groups maintained a significant ALT reduction vs. control following multivariable adjustment and propensity score weighting. Greater ALT reductions were seen with higher baseline ALT for both the SGLT2 inhibitor treatment groups.
SGLT2 inhibitors canagliflozin and dapagliflozin resulted in a weight and A1c-independent reduction of ALT levels compared to incretin agents, with a dose-response observed at higher baseline ALT levels. Further studies investigating the differential effects of these drug classes on NAFLD, and insulin/glucagon levels as potential mechanism explaining these differences, should be performed.
新型降糖药物对 2 型糖尿病（T2D）相关非酒精性脂肪性肝病（NAFLD）标志物的影响，其幅度和独立性存在不一致。这项大型回顾性研究调查了与参考对照组相比，新型 T2D 药物治疗起始后患者丙氨酸氨基转移酶（ALT）水平的变化。
我们研究了来自加拿大大型糖尿病登记处的 T2D 患者，这些患者在接受卡格列净、达格列净、利拉鲁肽、西格列汀或不再接受糖尿病治疗的基础上加用了这些药物。逐步多元回归用于确定糖化血红蛋白（HbA1c）和体重变化与 ALT 的相关性。采用倾向评分加权法平衡治疗组间的基线特征。
共有 3667 名患者符合研究标准。与肠促胰岛素药物（利拉鲁肽：-2.1U/L，P<0.01；西格列汀：-1.8U/L，P<0.01）相比，钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂（卡格列净：-4.3U/L，P<0.01；达格列净：-3.5U/L，P<0.01）治疗后 ALT 水平（平均随访 4.8 个月）更低。与对照组相比，SGLT2 抑制剂治疗组在多变量调整和倾向评分加权后仍能持续显著降低 ALT。对于 SGLT2 抑制剂治疗组，较高的基线 ALT 与更大的 ALT 降低相关。
与肠促胰岛素药物相比，SGLT2 抑制剂卡格列净和达格列净可在不依赖体重和糖化血红蛋白的情况下降低 ALT 水平，并且在较高的基线 ALT 水平观察到剂量反应。应开展进一步的研究，以探讨这些药物类别对 NAFLD 的不同影响，以及胰岛素/胰高血糖素水平作为解释这些差异的潜在机制。
