TY - JOUR
T1 - Impact of sodium-glucose cotransporter-2 inhibitors on aging biomarkers and plasma ceramide levels in type 2 diabetes
T2 - beyond glycemic control
AU - Shalaby, Youssef M.
AU - Nakhal, Mohammed Moutaz
AU - Afandi, Bachar
AU - Al-Zohily, Bashar
AU - Majed, Lina
AU - Kumar, Kukkala Kiran
AU - Emerald, Bright Starling
AU - Sadek, Bassem
AU - Akour, Amal
AU - Akawi, Nadia
N1 - Publisher Copyright:
© 2025 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
PY - 2025
Y1 - 2025
N2 - Background: Aging is a complex biological process marked by the decline of physiological functions and heightened susceptibility to chronic illnesses, notably cardiometabolic disorders. Ceramides (Cer) are lipid derivatives linked to aging and metabolic diseases. Sodium-Glucose Cotransporter-2 inhibitors (SGLT2i), widely used in managing type 2 diabetes, have an unclear impact on aging biomarkers and Cer profiles. Objective: This study explored the association between SGLT2i use, plasma Cer levels (CerC16:0, CerC18:0, CerC22:0, CerC24:0, and CerC24:1), and aging biomarkers—Human Insulin-Like Growth Factor 1 (IGF-1), mammalian target of rapamycin (mTOR), 5-Methylcytosine (5MC), and Human H2AFX (Histone H2AX) in patients with type 2 diabetes mellitus (T2DM). Methods: In this retrospective study, 95 participants were divided into three groups: patients on SGLT2i (n = 34), patients on non-SGLT2i anti-diabetic treatments (n = 36), and healthy controls (n = 25). Plasma Cer and aging biomarkers were quantified using Liquid Chromatography with tandem mass spectrometry (LC–MS–MS) and ELISA, respectively. Principal component analysis (PCA) assessed group-based clustering, while ANCOVA evaluated group differences with confounder adjustment. Results: SGLT2i-treated patients showed significantly lower CerC16:0, CerC22:0, and CerC24:1 levels (p < 0.01) and decreased 5MC and H2AX (p < 0.05) compared to non-SGLT2i patients. IGF-1 was significantly elevated in the SGLT2i group (p < 0.01), suggesting a possible protective effect on metabolic health. PCA distinguished control from diabetic groups but revealed overlap between SGLT2i and non-SGLT2i groups. Conclusion: Beyond glucose control, SGLT2i may improve plasma Cer and aging markers in diabetic patients, supporting their broader therapeutic potential in aging and age-related diseases. Further large-scale studies are warranted to confirm these effects and underlying mechanisms.
AB - Background: Aging is a complex biological process marked by the decline of physiological functions and heightened susceptibility to chronic illnesses, notably cardiometabolic disorders. Ceramides (Cer) are lipid derivatives linked to aging and metabolic diseases. Sodium-Glucose Cotransporter-2 inhibitors (SGLT2i), widely used in managing type 2 diabetes, have an unclear impact on aging biomarkers and Cer profiles. Objective: This study explored the association between SGLT2i use, plasma Cer levels (CerC16:0, CerC18:0, CerC22:0, CerC24:0, and CerC24:1), and aging biomarkers—Human Insulin-Like Growth Factor 1 (IGF-1), mammalian target of rapamycin (mTOR), 5-Methylcytosine (5MC), and Human H2AFX (Histone H2AX) in patients with type 2 diabetes mellitus (T2DM). Methods: In this retrospective study, 95 participants were divided into three groups: patients on SGLT2i (n = 34), patients on non-SGLT2i anti-diabetic treatments (n = 36), and healthy controls (n = 25). Plasma Cer and aging biomarkers were quantified using Liquid Chromatography with tandem mass spectrometry (LC–MS–MS) and ELISA, respectively. Principal component analysis (PCA) assessed group-based clustering, while ANCOVA evaluated group differences with confounder adjustment. Results: SGLT2i-treated patients showed significantly lower CerC16:0, CerC22:0, and CerC24:1 levels (p < 0.01) and decreased 5MC and H2AX (p < 0.05) compared to non-SGLT2i patients. IGF-1 was significantly elevated in the SGLT2i group (p < 0.01), suggesting a possible protective effect on metabolic health. PCA distinguished control from diabetic groups but revealed overlap between SGLT2i and non-SGLT2i groups. Conclusion: Beyond glucose control, SGLT2i may improve plasma Cer and aging markers in diabetic patients, supporting their broader therapeutic potential in aging and age-related diseases. Further large-scale studies are warranted to confirm these effects and underlying mechanisms.
KW - Aging biomarkers
KW - SGLT2i
KW - cardiometabolic diseases
KW - ceramide
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U2 - 10.1080/07853890.2025.2496795
DO - 10.1080/07853890.2025.2496795
M3 - Article
C2 - 40289660
AN - SCOPUS:105003996418
SN - 0785-3890
VL - 57
JO - Annals of Medicine
JF - Annals of Medicine
IS - 1
M1 - 2496795
ER -
