■ 学会名
The 22nd International Congress of Endocrinology (ICE2026) / The 99th Annual Congress of The Japan Endocrine Society (JES2026)

■ 発表日
2026/06/03

■ 筆頭演者
Yuichi Nishioka
Department of Public Health, Health Management and Policy, Nara Medical University
Department of Diabetes and Endocrinology, Nara Medical University Hospital

■ 共同演者
Yuichi Nishioka, Saki Takeshita, Emiri Morita, Kuniaki Ozaki, Fumika Kamitani, Takako Mohri, Hiroki Nakajima, Shin Urai, Yukako Kurematsu, Tomoya Myojin, Tomoaki Imamura, Yutaka Takahashi
¹ Department of Public Health, Health Management and Policy, Nara Medical University
² Department of Diabetes and Endocrinology, Nara Medical University Hospital
³ Department of Community Health & Preventive Medicine, Hamamatsu University School of Medicine

■ 発表形態
Poster

■ 要旨
Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are antidiabetic agents with cardiovascular and renal benefits. Recent report published in Nature Aging showed their senolytic activity and lifespan extension in progeroid mice, suggesting a potential geroprotective effect. Yet, the effect in humans remains unclarified.
Methods: Using a Japanese claims DeSC database (17 million individuals, 2014–2024), we applied Target Trial Emulation with a novel exact-matching method developed by us. This approach minimizes bias and type I error by fully matching sex, birthdate, observation start, drug prescriptions, comorbidities (renal failure, heart failure, diabetes), and Charlson Comorbidity Index.
Results: Among 224,010 SGLT2 inhibitor users (58.7% male, mean age 72.2), mortality was significantly lower than that in matched non-users (HR 0.93, 95% CI 0.90–0.96). The mortality was also reduced compared with biguanide (P = 0.03) and DPP-4 inhibitor users (P < 0.01), respectively. Discussion: This is the first empirical evidence of lifespan extension by SGLT2 inhibitors in humans, achieved through rigorous confounder adjustment with new method. Our findings bridge animal studies with population-level data, highlighting SGLT2 inhibitors as a potential geroprotector beyond diabetes treatment. Limitations: Although every including factors were adjusted, observational design cannot exclude unmeasured confounding. Long-term randomized prospective trials are needed for generalizability of the method requires caution. Conclusion: These data demonstrated that SGLT2 inhibitors prolong life span in humans. These data also suggested a novel therapeutic avenue for aging-related diseases. Future international cohorts and intervention trials are necessary to establish their role as geroprotective agents.