Scholarlink

Background <p>Oxidative stress and inflammation contribute to diabetes-related organ damage beyond hyperglycemia. Imeglimin and sodium-glucose cotransporter 2 inhibitors may modulate redox balance through distinct mitochondrial pathways, but their comparative effects on organ-level stress remain unclear.</p> Objective <p>To compare the effects of imeglimin and empagliflozin on oxidative stress, inflammation, and subclinical organ stress markers in type 2 diabetes mellitus (T2DM).</p> Methods <p>In this 24-week, prospective, randomized, open-label study, people with T2DM received imeglimin (<i>n</i> = 34) or empagliflozin (<i>n</i> = 42). Changes in urinary 8-hydroxy-2′-deoxyguanosine (u8-OHdG) and liver-type fatty acid-binding protein (L-FABP) were assessed as co-primary endpoints. Secondary endpoints included serum diacron-reactive oxygen metabolites (d-ROM), biological antioxidant potential (BAP), serum 8-OHdG (s8-OHdG), tumor necrosis factor receptors 1/2 (TNFR1/2), and organ stress markers: N-terminal pro-brain natriuretic peptide (NT-proBNP), Fibrosis-4 index (FIB-4), and cardio-ankle vascular index (CAVI).</p> Results <p>u8-OHdG levels increased significantly, while L-FABP levels were not significantly changed at 24 weeks, suggesting a systemic rather than renal oxidative response. Only empagliflozin improved FIB-4, NT-proBNP, and CAVI values. Both treatments reduced TNFR1/2 values and increased BAP values. In the empagliflozin group, univariate analysis showed that ΔFIB-4 was positively correlated with ΔTNFR1 and ΔTNFR2, while ΔNT-proBNP and ΔCAVI showed inverse trends with ΔBAP. Multivariate analysis identified changes in hemoglobin A1c and Δd-ROM as independent predictors of FIB-4 improvement, and empagliflozin use as an independent predictor of ΔCAVI.</p> Conclusion <p>Both agents induced antioxidant and anti-inflammatory responses. In addition, empagliflozin improved cardiac, hepatic, and vascular stress markers, possibly through its antioxidant and anti-inflammatory effects.</p> Trial registration <p>Japan Registry of Clinical Trials (registration number jRCT1061230069, date of registration October 24, 2023).</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

Comparative effects of Imeglimin and empagliflozin on the redox-inflammation-organ stress axis in type 2 diabetes: a randomized controlled trial

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月9日

查看全文
  • Toshiki Otoda,
  • Akiko Sekine,
  • Ryoko Uemoto,
  • Taiki Hori,
  • Tomoyo Hara,
  • Motoyuki Tamaki,
  • Shingen Nakamura,
  • Tomoyuki Yuasa,
  • Tadateru Takayama,
  • Munehide Matsuhisa,
  • Ken-ichi Aihara

摘要

Background

Oxidative stress and inflammation contribute to diabetes-related organ damage beyond hyperglycemia. Imeglimin and sodium-glucose cotransporter 2 inhibitors may modulate redox balance through distinct mitochondrial pathways, but their comparative effects on organ-level stress remain unclear.

Objective

To compare the effects of imeglimin and empagliflozin on oxidative stress, inflammation, and subclinical organ stress markers in type 2 diabetes mellitus (T2DM).

Methods

In this 24-week, prospective, randomized, open-label study, people with T2DM received imeglimin (n = 34) or empagliflozin (n = 42). Changes in urinary 8-hydroxy-2′-deoxyguanosine (u8-OHdG) and liver-type fatty acid-binding protein (L-FABP) were assessed as co-primary endpoints. Secondary endpoints included serum diacron-reactive oxygen metabolites (d-ROM), biological antioxidant potential (BAP), serum 8-OHdG (s8-OHdG), tumor necrosis factor receptors 1/2 (TNFR1/2), and organ stress markers: N-terminal pro-brain natriuretic peptide (NT-proBNP), Fibrosis-4 index (FIB-4), and cardio-ankle vascular index (CAVI).

Results

u8-OHdG levels increased significantly, while L-FABP levels were not significantly changed at 24 weeks, suggesting a systemic rather than renal oxidative response. Only empagliflozin improved FIB-4, NT-proBNP, and CAVI values. Both treatments reduced TNFR1/2 values and increased BAP values. In the empagliflozin group, univariate analysis showed that ΔFIB-4 was positively correlated with ΔTNFR1 and ΔTNFR2, while ΔNT-proBNP and ΔCAVI showed inverse trends with ΔBAP. Multivariate analysis identified changes in hemoglobin A1c and Δd-ROM as independent predictors of FIB-4 improvement, and empagliflozin use as an independent predictor of ΔCAVI.

Conclusion

Both agents induced antioxidant and anti-inflammatory responses. In addition, empagliflozin improved cardiac, hepatic, and vascular stress markers, possibly through its antioxidant and anti-inflammatory effects.

Trial registration

Japan Registry of Clinical Trials (registration number jRCT1061230069, date of registration October 24, 2023).