Gender Differences in Cardiac Function Following Three-Month Administration of Tofogliflozin in Patients With Diabetes Mellitus

Higashikawa, Toshihiro; Ito, Tomohiko; Mizuno, T.; Ishigami, Keiichiro; Kohori, Masaru; Mae, Kunihiro; Usuda, Daisuke; Takeshima, Kento; Takagi, Susumu; Izumida, Toshihide; Yamada, Shinya; Kuroki, Kengo; Sangen, Ryusho; Saito, Atsushi; Iguchi, Masaharu; Kamasaki, Yuji; Nakahashi, Takeshi; Fukuda, Akira; Kanda, Tsugiyasu; Okuro, Masashi

doi:10.14740/jocmr4278

Cited by 5 publications

(6 citation statements)

References 48 publications

(60 reference statements)

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“…Third, other residual confounding factors, such as genetics, physical activity or dietary factors, are also not included in the NHI data. However, our results are consistent with those of previous validation studies [ 19 , 20 ]. Fourth, Three types of SGLT2i (Empagliflozin, Dapagliflozin, and Canagliflozin) were launched since May 2016 and used till the end of the study (December 31, 2019).…”

Section: Discussionsupporting

confidence: 93%

The association between SGLT2 inhibitors and new-onset acute coronary syndrome in the elderly: a population-based longitudinal cohort study

Lin,

Lee,

Cheng

et al. 2023

Diabetol Metab Syndr

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Background Several observational cohorts and meta-analytical studies on humans have shown that users of sodium-glucose cotransporter-2 inhibitors (SGLT2is) have a lower risk for new-onset acute coronary syndrome (ACS) than nonusers. However, some studies, including randomized clinical trials, reported the opposite results. This study aimed to investigate the impacts of a SGLT2i on new-onset ACS in a population. Methods We conducted a retrospective population-based cohort study involving 56,356 subjects who received SGLT2i therapy and 112,712 patients who did not receive SGLT2i therapy between May 1, 2016 and December 31, 2019. The outcome was the risk of new-onset ACS. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals for associations between SGLT2i use and ACS risk. Results A total of 670 and 1408 ACS events occurred in SGLT2i users and nonusers, respectively, during a follow-up of 3.7 years. SGLT2i use was associated with a nonsignificantly lower risk of ACS (adjusted HR 0.95, 95%confidence intervals (CI 0.87–1.04, P = 0.3218). We confirmed the robustness of these results through a propensity score 1:1 matching analysis. The results of the subgroup analysis of the subtype of the SGLT2i treatments were consistent with the main findings. An increased risk for the incidence of ACS in male and older (> 70 years) patients were also found. Conclusions In this population-based cohort study, we found that SGLT2i use is associated with a nonsignificantly decreased risk of ACS. No difference in the SGLT2i subtype was observed in subgroup analyses. However, the results of this study indicated an increased risk for the incidence of ACS in male and older (> 70 years) patients.

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Section: Discussionsupporting

confidence: 93%

The association between SGLT2 inhibitors and new-onset acute coronary syndrome in the elderly: a population-based longitudinal cohort study

Lin,

Lee,

Cheng

et al. 2023

Diabetol Metab Syndr

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“…In addition, our previous data presented no change in IVCmax (inferior vena cava maximal diameter), [ 13 ] indicating that there is no change in the volume of the vessel, that is, no intravascular dehydration. [ 28 ] Furthermore, we observed no changes in intracellular and extracellular body fluids.…”

Section: Discussionmentioning

confidence: 95%

“…Herein, we performed a retrospective study to investigate the effect of tofogliflozin, an SGLT2 inhibitor, on the HPA system in elderly patients with T2DM. This study included elderly patients diagnosed with T2DM at the Kanazawa Medical University Himi Municipal Hospital from April 2017 to March 2019, as described previously [11–13] . Briefly, elderly patients aged ≥65 years received a single 20 mg dose of tofogliflozin daily for 3 months.…”

Section: Methodsmentioning

confidence: 99%

“…This study included elderly patients diagnosed with T2DM at the Kanazawa Medical University Himi Municipal Hospital from April 2017 to March 2019, as described previously. [11][12][13] Briefly, elderly patients aged ≥65 years received a single 20 mg dose of tofogliflozin daily for 3 months. Patients with significant comorbidities were excluded.…”

Section: Methodsmentioning

confidence: 99%

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Effects of tofogliflozin on adrenocorticotropic hormone, renin and aldosterone, and cortisol levels in elderly patients with diabetes mellitus

et al. 2021

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Adrenocorticotropic hormone (ACTH) and cortisol reportedly play a role in glycemic control in patients with type 2 diabetes mellitus (T2DM); however, the underlying mechanism remains controversial. We retrospectively investigated the effect of tofogliflozin on serum ACTH and cortisol levels in elderly patients with T2DM.Patients received 20 mg tofogliflozin daily for 3 months. Serum ACTH and cortisol levels were measured at baseline, as well as after 1 month and 3 months of tofogliflozin therapy.Serum ACTH levels were significantly reduced 3 months after tofogliflozin treatment (P < .01). Additionally, serum cortisol levels were reduced 3 months after tofogliflozin treatment, demonstrating borderline significance (P = .05). The higher body mass index (BMI; ≥25 kg/m2) group showed higher ACTH and cortisol levels than the lower BMI (<25 kg/m2) group, with borderline significance (P = .05). Renin levels were significantly increased 1 month after treatment (P < .05), maintaining serum aldosterone levels in parallel with the extracellular fluid.Our findings suggested that tofogliflozin decreased both serum ACTH and cortisol levels, with higher levels observed in the high BMI group. Tofogliflozin increased serum renin levels while maintaining serum aldosterone and extracellular fluid levels. Collectively, tofogliflozin could affect the hypothalamic-pituitary-adrenal pathway in patients with T2DM, especially in the low BMI group.

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“…[11] Soga et al [12] reported that dapagliflozin improved atrial volume index (LAVI), left ventricular mass index (LVMI), and E/e' in a few days and maintained it up to 3 months. Higashikawa et al, [13,14] Tochiya et al, [15] and Otagaki et al, [16] reported that tofogliflozin also improved E/e'. A meta-analysis also reported improvement in EF, E/e', and global longitudinal strain (GLS) as class effects of SGLT2 inhibitors.…”

Section: Introductionmentioning

confidence: 98%

Effects of 6-month administration of tofogliflozin on cardiac function in elderly patients with heart failure with preserved ejection fraction: A retrospective study of a patient cohort

Higashikawa,

Ito,

Mizuno

et al. 2024

Medicine

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Patients with type 2 diabetes mellitus are frequently hospitalized for heart failure. The ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/e’), measured by echocardiography, is a simple and convenient indicator of diastolic dysfunction. Various large clinical trials have reported that sodium glucose transporter-2 inhibitor therapy reduced cardiovascular events and hospitalizations in heart failure patients. We examined the effect of tofogliflozin on various physiological and cardiac function. A retrospective analysis was performed on elderly patients aged 65 years or older with type 2 diabetes mellitus attending Himi Municipal Hospital who were taking oral tofogliflozin 20 mg/day. Measurement of physiological and hormonal variables, blood sampling, and echocardiographic evaluations at 0, 1, 3, and 6 months were performed on those with ejection fraction (EF) of 40% or greater at the time of treatment. Statistical analysis was performed using t-tests and mixed-effects models, with brain natriuretic peptide less than or not less than 100 pg/mL, estimated glomerular filtration rate (eGFR) less than or not less than 50 mL/min/1.73 m2, and diuretics administered or not. Hypoglycemic effects were observed at 0, 1, 3, and 6 months. At each time point, EF was retained and E/e’ was significantly reduced. On the other hand, most physiological parameters and laboratory results showed no clinical abnormalities. Mixed-effects models showed time-dependent reduction of E/e’ in high/low brain natriuretic peptide, high/low eGFR, with or without diuretics between baseline and at 6 months. The interaction with time was significant in high/low eGFR. Tofogliflozin was shown to improve E/e’, a measure of diastolic function, while maintaining EF, with hypoglycemic effects and no clinical side effects.

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Gender Differences in Cardiac Function Following Three-Month Administration of Tofogliflozin in Patients With Diabetes Mellitus

Cited by 5 publications

References 48 publications

The association between SGLT2 inhibitors and new-onset acute coronary syndrome in the elderly: a population-based longitudinal cohort study

The association between SGLT2 inhibitors and new-onset acute coronary syndrome in the elderly: a population-based longitudinal cohort study

Effects of tofogliflozin on adrenocorticotropic hormone, renin and aldosterone, and cortisol levels in elderly patients with diabetes mellitus

Effects of 6-month administration of tofogliflozin on cardiac function in elderly patients with heart failure with preserved ejection fraction: A retrospective study of a patient cohort

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