Effect of henagliflozin on aging biomarkers in patients with type 2 diabetes: A multicenter, randomized,
Jie Zhang1, Wei Cai2, Danfeng Liu2
1Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China; Jiangxi Clinical Research Center for Endocrine and Metabolic Disease, Nanchang, Jiangxi 330006, People's Republic of China; Jiangxi Branch of National Clinical Research Center for Metabolic Disease, Nanchang, Jiangxi 330006, People's Republic of China.
Abstract:
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).
Insights
Henagliflozin, a sodium-glucose cotransporter-2 inhibitor, significantly increased telomere length and improved glucose metabolism in a 26-week trial. This suggests potential anti-aging benefits by influencing key aging biomarkers.
Area of Science:
- Endocrinology and Metabolism
- Aging Research
- Immunology
Background:
- Sodium-glucose cotransporter-2 (SGLT2) inhibitors are explored as caloric restriction mimetics.
- Limited clinical data exist on SGLT2 inhibitors' impact on aging biomarkers.
Purpose of the Study:
- To evaluate the effects of henagliflozin on aging biomarkers in individuals with type 2 diabetes.
- To investigate henagliflozin's influence on telomere length, metabolic markers, and immune cell function.
Main Methods:
- Multicenter, randomized, double-blind, placebo-controlled trial.
- 150 participants with type 2 diabetes received henagliflozin (10 mg/day) or placebo for 26 weeks.
- Primary endpoint: change in telomere length; secondary endpoints: metabolic and immune markers.
Main Results:
- Henagliflozin significantly increased telomere length compared to placebo.
- Improvements observed in glucose metabolism, insulin-like growth factor-binding protein-3, and β-hydroxybutyrate levels.
- Increased granzyme B expression in cytotoxic T lymphocytes and enhanced thiamine metabolism.
Conclusions:
- Henagliflozin demonstrates potential anti-aging effects by modulating telomere length and immune function.
- The drug influences multiple pathways, including metabolic and cellular aging markers.
- Further research is warranted to confirm these anti-aging properties in diverse populations.
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