Influence of Age on the Effects of Sodium-Glucose Cotransporter 2 Inhibitors in Japanese Patients With Type 2 Diabetes Mellitus

Masataka Kusunoki, Fumiya Hisano, Shinichi Matsuda, Naomi Wakazono, Kazuhiko Tsutsumi, Tetsuro Miyata


Background: Selective inhibitors of sodium-glucose cotransporter 2 (SGLT2) inhibitors have been reported to improve glucose metabolism, lipid metabolism and liver dysfunction in patients with type 2 diabetes mellitus. However, few studies have investigated if the effects of this class of drugs vary according to the age of the patients. This study was conducted to determine the influence of age on the effects of SGLT2 inhibitors in Japanese patients with diabetes mellitus.

Methods: SGLT2 inhibitors were administered for 6 months to 199 patients with type 2 diabetes mellitus. The body weight, body mass index (BMI), visceral fat area, serum glucose, hemoglobin A1c (HbA1c), blood lipid levels, serum uric acid, liver function parameters, and bone mineral density were measured before and after 6 months of treatment, and regression analysis was performed to examine the relationship between age and the effects of SGLT2 inhibitors.

Results: The results of the regression analysis showed that the effects of SGLT2 inhibitors on the serum levels of high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (gamma-GTP) were influenced by the patient age. The effect of SGLT2 inhibitors in increasing the serum HDL-C was more pronounced in older patients. There was an interaction between age and the baseline levels of the serum AST and gamma-GTP; reductions of the serum AST and gamma-GTP levels by SGPLT2 inhibitors were more pronounced in younger patients with higher baseline levels of these parameters, but not pronounced in aged patients.

Conclusions: The effects of SGLT2 inhibitor treatment on the serum HDL-C, AST and gamma-GTP levels were affected by the patient age: their beneficial effect on the serum HDL-C increased with the patient age and their effects in reducing the serum AST and gamma-GTP decreased with the patient age. The effects of SGLT2 inhibitor treatment on the blood glucose and serum HbA1c were not affected by the patient age, suggesting that SGLT2 inhibitors can be used as antidiabetic drugs in patients over a wide age range, from the young to the elderly.

J Endocrinol Metab. 2022;12(2):53-58


SGLT2 inhibitor; Aging; Glycemic control; Lipid metabolism; Hepatic function

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