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Sleep apnea (SA) is prevalent among patients with heart failure (HF) and contributes to a poor prognosis. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated efficacy in reducing the risk of serious clinical events in patients with HF. Additionally, SGLT2 inhibitors may reduce the risk of incident SA and mitigate its severity in patients with cardiovascular disease and T2DM. We aimed to investigate whether the SGLT2 inhibitor tofogliflozin reduced the severity of SA, as assessed using the apnea-hypopnea index (AHI), in patients with HF and T2DM and whether a decrease in AHI correlates with changes in body composition and cardiorenal function parameters. This is a single-arm, prospective pathophysiologic study involving patients with HF, T2DM, and SA, defined as having an AHI of 15 events/h and more. SA was assessed using polysomnography. Changes in AHI before and 6 months after starting oral administration of tofogliflozin (20 mg) were assessed. Additionally, body composition and cardiorenal functions were assessed before and 6 months after tofogliflozin administration. Ten patients with HF, T2DM, and SA were finally enrolled (60% men, 66.9 ± 13.4 years). Tofogliflozin reduced AHI from 43.2 [30.2] to 35.3 [13.1] events/h (p = 0.024) at 6 months. Hemoglobin A1c, body weight, and body water content decreased significantly. However, no significant changes were observed in the cardiorenal function parameters. A linear relationship was observed between the changes in body water content and AHI (r = 0.642, p = 0.045). Tofogliflozin reduced AHI, possibly associated with a reduction in body water content.
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http://dx.doi.org/10.1038/s41440-024-01982-3 | DOI Listing |
Hypertens Res
July 2025
Division of Nephrology, Endocrinology, and Metabolism, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Sodium-glucose co-transporter 2 (SGLT2) inhibitors promote weight loss in patients with type 2 diabetes mellitus; however, the underlying mechanisms remain unknown. This study investigated the role of renal autonomic nerves in SGLT2 inhibitor-induced lipolysis and body weight reduction by utilizing the renal denervation technique. The results indicated that renal autonomic nerves mediated lipolysis in mice fed a high-fat diet following treatment with tofogliflozin, an SGLT2 inhibitor.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
July 2025
Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Introduction: Pancreatic beta cells undergo metabolic remodeling in response to metabolic overload, but the functional significance of this remains unclear. 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) is a glycolytic regulator that may play a role in beta cell adaptation under acute metabolic stress. This study aimed to investigate the involvement of PFKFB3 in beta cell function under such stress.
View Article and Find Full Text PDFEur J Pharmacol
June 2025
Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon, 24341, South Korea. Electronic address:
Tofogliflozin is a sodium-glucose cotransporter 2 inhibitor widely used to treat type 2 diabetes mellitus, but it also exhibits cardio-protective effects. This study investigated the vasodilatory action of tofogliflozin using rabbit femoral artery rings pre-contracted with phenylephrine (1 μM). The results showed the concentration-dependent induction of vasodilation by tofogliflozin, a response that remained unchanged following endothelial removal, pretreatment with the nitric oxide synthase inhibitor L-NAME (100 μM), or the inhibition of low- and intermediate-conductance Ca-activated K channels using apamin (1 μM) in combination with TRAM-34 (1 μM).
View Article and Find Full Text PDFJ Diabetes Investig
April 2025
Department of Diabetes and Endocrinology, University of Yamanashi Hospital, Yamanashi, Japan.
Aims/introduction: Patients with type 2 diabetes are at high risk of developing steatotic liver disease (SLD). Weight loss has proven effective in treating metabolic dysfunction-associated steatotic liver disease (MASLD) in obese patients with type 2 diabetes, with sodium-glucose cotransporter 2 (SGLT2) inhibitors showing promising results. However, lean MASLD is more prevalent in Japan, necessitating alternative approaches to body weight reduction.
View Article and Find Full Text PDFCurr Vasc Pharmacol
August 2025
Dental Post Graduate Training Department, PHCC, Manama, Kingdom of Bahrain.
Introduction: Sodium Glucose cotransporter-2 inhibitors (SGLT2is) possess pleiotropic effects, such as antioxidant, antifibrotic, anti-inflammatory, and vascular remodeling activities. Considering the lack of literature, a network meta-analysis was conducted to explore the impact of SGLT2is on endothelial dysfunction and arterial stiffness in the diabetic population.
Methods: Electronic databases were searched to identify randomized clinical trials evaluating the effects of SGLT2is on outcomes, such as Flow-mediated Vasodilation (FMV), Pulse Wave Velocity (PWV), and Augmentation Index (AIx).