Effect of henagliflozin on aging biomarkers in patients with type 2 diabetes: A multicenter, randomized, double-blind, placebo-controlled study
Sodium-glucose cotransporter-2 inhibitors have been proposed as caloric restriction mimetics with potential anti-aging effects. However, clinical data on their influence on aging biomarkers are limited. In this multicenter, randomized, double-blind, placebo-controlled trial, 150 participants with type 2 diabetes are randomized (1:1) to receive oral henagliflozin (10 mg/day) or placebo for 26 weeks. Compared with placebo, henagliflozin significantly increases telomere length (primary endpoint), insulin-like growth factor-binding protein-3 levels, and β-hydroxybutyrate levels and improves glucose metabolism. Immune analysis reveals that henagliflozin significantly increases granzyme B expression in cytotoxic T lymphocytes (CTLs) and tends to increase perforin expression in CTLs and perforin and granzyme B expression in total T lymphocytes. Metabolomic analysis shows that henagliflozin induces changes in various metabolites, including increased thiamine levels and enhanced thiamine metabolism. These findings suggest that henagliflozin may exert anti-aging effects through multiple pathways. This study is registered at Chinese Clinical Trial Registry (ChiCTR2300068127).
Authors
- Huaxia Gan
- Lingyan Zhu (ORCID: https://orcid.org/0009-0005-6184-7170)
- Guanjun Huang
- G Luo
- Jixiong Xu (ORCID: https://orcid.org/0000-0001-9825-3003)
- Danfeng Liu (ORCID: https://orcid.org/0000-0002-4630-091X)
- Yuqing Huang (ORCID: https://orcid.org/0000-0002-3182-1798)
- Jie Zhang (ORCID: https://orcid.org/0000-0003-1413-2293)
- Jianping Guo (ORCID: https://orcid.org/0000-0002-5031-3510)
- Yu Liu (ORCID: https://orcid.org/0000-0001-8359-6732)
- Feng Qiu (ORCID: https://orcid.org/0000-0003-0611-1687)
- Chenxi Li (ORCID: https://orcid.org/0000-0001-9660-9256)
- Yan Zhang (ORCID: https://orcid.org/0000-0001-9126-4922)
- Yan Zhou (ORCID: https://orcid.org/0000-0001-9402-1109)
- Zheng He (ORCID: https://orcid.org/0000-0002-2357-1936)
- Chengbi Yu
- Shuping Xiong (ORCID: https://orcid.org/0000-0002-6499-2702)
- Youping Wang (ORCID: https://orcid.org/0000-0002-7119-782X)
- Meiling Yu
- H X Ke
- Wei Cai (ORCID: https://orcid.org/0009-0002-6214-9217)
- Liangming Hu
- Nianye Zheng
Institutions
- Shangrao Normal University (CN)
- Jiangxi University of Traditional Chinese Medicine (CN)
- Jinggangshan University (CN)
- Jiujiang First People's Hospital (CN)
- Jingdezhen University (CN)
- Jiangxi Provincial People's Hospital (CN)
- Jining Traditional Chinese Medicine Hospital (CN)
- Zoucheng People's Hospital (CN)
- Jiangxi Pingxiang People's Hospital (CN)
- Fujian Provincial People's Hospital (CN)
- The First People's Hospital of Jiangxia District (CN)
- Cixian People's Hospital (CN)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2025-09-01
- DOI
- https://doi.org/10.1016/j.xcrm.2025.102331
- Citations
- 1
- Primary Topic
- Pancreatic function and diabetes
- Type
- article
- Field-Weighted Citation Impact
- 2.01
Funders
- Jiangsu Hengrui Medicine
- Nanchang University