选择性SGLT2抑制剂恩格列净对2型糖尿病患者脂肪因子谱的体重无关改善作用

Weight-independent amelioration of adipokine profile by enavogliflozin, a selective SGLT2 inhibitor, in patients with type 2 diabetes.

作者信息

Lyu Young Sang, Lee Hansol, Kim Kyung-Soo, Hong Sangmo, Park Cheol-Young

机构信息

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chosun University Hospital, Gwangju, Republic of Korea.

Daewoong Pharmaceutical Co., Ltd., Seoul, Republic of Korea.

出版信息

Cardiovasc Diabetol. 2025 Aug 31;24(1):355. doi: 10.1186/s12933-025-02917-z.

DOI:10.1186/s12933-025-02917-z

PMID:40887579

Abstract

BACKGROUND AND OBJECTIVE

The metabolic benefits of sodium-glucose co-transporter 2 inhibitors in clinical application are well established; however, there is dearth of knowledge on their impact on adipokine regulation. This study investigated the effect of enavogliflozin on adiponectin and leptin in patients with type 2 diabetes.

METHODS

This secondary analysis of a phase III randomized, double-blind, placebo-controlled trial evaluated changes in serum adiponectin and leptin over 24 weeks. Analysis of covariance was used with baseline values and weight change as covariates to examine whether the effects of enavogliflozin persisted after adjusting for weight change. Correlations between adipokine changes and key metabolic parameters were also assessed.

RESULTS

Over the 24 weeks, the enavogliflozin group showed increased adiponectin levels with a least squares (LS) mean difference of 0.98 mg/L compared with the placebo group, while leptin levels showed a significant decrease with an LS mean difference of -2.99 µg/L. Enavogliflozin significantly reduced leptin levels over 24 weeks after adjusting for weight change; however, adiponectin changes were not significant after adjusting for weight change. Adiponectin levels significantly increased across weight loss categories, but leptin showed no significant differences. Leptin changes over 24 weeks significantly were positively correlated with changes in homeostasis model assessment of insulin resistance and homeostasis model assessment of β-cell function but significantly negatively correlated with changes in serum ketone and urinary glucose-to-creatinine ratio.

CONCLUSIONS

Enavogliflozin treatment decreased leptin over 24 weeks in patients with type 2 diabetes, and this effect remained significant after adjusting for weight change, suggesting an improved adipokine profile. Reductions in leptin were also associated with improvements in insulin resistance and increases in serum ketone levels. These results highlight enavogliflozin as a potential treatment beyond glycemic control, offering additional benefits in managing metabolic dysregulation associated with type 2 diabetes.

TRIAL REGISTRATION

Not applicable (post hoc analysis).

摘要

背景与目的

钠-葡萄糖协同转运蛋白2抑制剂在临床应用中的代谢益处已得到充分证实；然而，关于其对脂肪因子调节的影响，目前仍知之甚少。本研究调查了恩格列净对2型糖尿病患者脂联素和瘦素的影响。

方法

本项对一项III期随机、双盲、安慰剂对照试验的二次分析评估了24周内血清脂联素和瘦素的变化。采用协方差分析，将基线值和体重变化作为协变量，以检验在调整体重变化后恩格列净的作用是否持续存在。还评估了脂肪因子变化与关键代谢参数之间的相关性。

结果

在24周内，恩格列净组的脂联素水平升高，与安慰剂组相比，最小二乘（LS）均值差异为0.98mg/L，而瘦素水平显著降低，LS均值差异为-2.99μg/L。在调整体重变化后，恩格列净在24周内显著降低了瘦素水平；然而，调整体重变化后脂联素的变化并不显著。脂联素水平在各体重减轻类别中均显著升高，但瘦素无显著差异。24周内瘦素的变化与胰岛素抵抗稳态模型评估和β细胞功能稳态模型评估的变化显著正相关，但与血清酮和尿葡萄糖与肌酐比值的变化显著负相关。