Scholarlink

Background <p>Dapagliflozin (DAPA) has shown major nephroprotective effects, improving kidney metabolism and oxigenation. Lipidomics and metabolomics are powerful tools for understanding such effects, providing a comprehensive look at how SGLT2 inhibitors might change the metabolic landscape beyond their primary glucose-lowering action. We investigated changes in plasma metabolomic/lipidomic profile and urinary excretion of metabolites that could occur independent of increased diuresis.</p> Methods <p>A two-armed, parallel-design, randomized clinical trial was conducted in subjects with type 2 diabetes and hypertension who received treatment with DAPA 10&#xa0;mg/day or hydrochlorothiazide 12.5&#xa0;mg/day for four weeks. Lipidomics and metabolomics were performed by high resolution mass spectrometry in fasting plasma and 24-hour urine samples collected before and after treatment.</p> Results <p>Compared to hydrochlorothiazide, DAPA significantly increased plasma isoleucine, methionine, citrate, β-hydroxybutyrate and decreased lactate. DAPA induced plasma lipid remodeling towards a significant raise in free fatty acids (FFAs) and some sphingomyelins and lysophosphatidylcholines containing these fatty acids. A significant change was observed in plasma medium- and short-chain acylcarnitines, positively correlated with changes in plasma FFAs and β-hydroxybutyrate. In addition, DAPA, but not hydrochlorothiazide, significantly increased 24-h urinary excretion of several amino-acids, lactate, TCA cycle metabolites, β-hydroxybutyrate and electrolytes, except for a decrease in malate excretion.</p> Conclusions <p>DAPA treatment has major effects on the plasma lipidomic and the urine metabolomic profiles, with significant increased renal excretion of several metabolites, especially amino-acids, independently of increased diuresis. These data offer insights into the complex metabolic pathways leading to kidney protection by SGLT2 inhibitors.</p> Clinical Trial Information <p>European Union Drug Regulating Authorities Clinical Trials No. 2015-004164-11.</p> Graphical abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Dapagliflozin modulates plasma lipidomic profile and urinary metabolite excretion in type 2 diabetes

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月30日

查看全文
  • Samantha Pezzica,
  • Filippo Pratesi,
  • Silvia Sabatini,
  • Fabrizia Carli,
  • Alessandro Mengozzi,
  • Anna Solini,
  • Amalia Gastaldelli

摘要

Background

Dapagliflozin (DAPA) has shown major nephroprotective effects, improving kidney metabolism and oxigenation. Lipidomics and metabolomics are powerful tools for understanding such effects, providing a comprehensive look at how SGLT2 inhibitors might change the metabolic landscape beyond their primary glucose-lowering action. We investigated changes in plasma metabolomic/lipidomic profile and urinary excretion of metabolites that could occur independent of increased diuresis.

Methods

A two-armed, parallel-design, randomized clinical trial was conducted in subjects with type 2 diabetes and hypertension who received treatment with DAPA 10 mg/day or hydrochlorothiazide 12.5 mg/day for four weeks. Lipidomics and metabolomics were performed by high resolution mass spectrometry in fasting plasma and 24-hour urine samples collected before and after treatment.

Results

Compared to hydrochlorothiazide, DAPA significantly increased plasma isoleucine, methionine, citrate, β-hydroxybutyrate and decreased lactate. DAPA induced plasma lipid remodeling towards a significant raise in free fatty acids (FFAs) and some sphingomyelins and lysophosphatidylcholines containing these fatty acids. A significant change was observed in plasma medium- and short-chain acylcarnitines, positively correlated with changes in plasma FFAs and β-hydroxybutyrate. In addition, DAPA, but not hydrochlorothiazide, significantly increased 24-h urinary excretion of several amino-acids, lactate, TCA cycle metabolites, β-hydroxybutyrate and electrolytes, except for a decrease in malate excretion.

Conclusions

DAPA treatment has major effects on the plasma lipidomic and the urine metabolomic profiles, with significant increased renal excretion of several metabolites, especially amino-acids, independently of increased diuresis. These data offer insights into the complex metabolic pathways leading to kidney protection by SGLT2 inhibitors.

Clinical Trial Information

European Union Drug Regulating Authorities Clinical Trials No. 2015-004164-11.

Graphical abstract