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AIMS/INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors effectively and safely reduce fasting and postprandial hyperglycemia while promoting weight loss. However, their unique mechanism of action contributes to concerns regarding their safety. We therefore carried out a large-scale, non-commercial, investigator-initiated study on the safety and effectiveness of the SGLT2 inhibitor tofogliflozin. MATERIALS AND METHODS: This multicenter, open-label, uncontrolled, prospective observational study was carried out at hospitals and clinics across Japan in participants aged ≥20 years who were SGLT2 inhibitor-naïve and had an established diagnosis of type 2 diabetes. The primary endpoint was adverse drug reactions (ADRs) of special interest. Secondary endpoints included all other ADRs and adverse events, glycated hemoglobin (HbA1c), and weight loss. RESULTS: The study, carried out from June 2014 through February 2020, enrolled 11,480 participants from 1,103 medical institutions; 6,967 participants completed the 104-week follow up. The most common ADRs of special interest were urinary and genital tract infections (1.53%), followed by volume depletion (1.25%). Hypoglycemia occurred in 27 participants (0.24%), adverse events in 1,054 (9.18%) and ADRs in 645 (5.62%). HbA1c decreased by 0.85% (95% confidence interval 0.82%-0.88%) and bodyweight decreased by 3.05 kg (95% confidence interval 2.94-3.17 kg). The HbA1c target was achieved by 51.70% of participants for target HbA1c <7.0%, 85.3% for <8.0% and 5.4% for <6.0% at week 104. CONCLUSIONS: Tofogliflozin was associated with only mild or moderate ADRs characteristic of SGLT2 inhibitors, with no unpredictable, new, serious, or high-incidence adverse events or ADRs. This independent study confirmed the safety and effectiveness of tofogliflozin in adult type 2 diabetes patients.
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AIMS/INTRODUCTION: Efficacy of long-term low-carbohydrate diets (LCD) to improve glycemic management for type 2 diabetes remains controversial. Thus, we investigated the association between long-term LCD and glycemic control in individuals with type 2 diabetes. MATERIALS AND METHODS: We searched PubMed, Embase and the Cochrane Database for articles published up to June 2023, and included randomized controlled trials conducted on LCD interventions for >12 months in adults with type 2 diabetes. Primary outcome was the difference in glycated hemoglobin between long-term LCD and control groups. Additionally, we evaluated the differences in changes in systolic and diastolic blood pressure, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, and weight between long-term LCD and control groups. RESULTS: Six studies were identified and met the inclusion criteria. This study did not show significant differences in changes in glycated hemoglobin between long-term LCD and control diets (standardized mean difference -0.11, 95% confidence interval -0.33 to 0.11, P = 0.32). As with glycemic control, there were no significant differences in the changes in weight loss, blood pressure, and low-density lipoprotein cholesterol between long-term LCD and control diets. However, long-term LCD were associated with greater elevation in high-density lipoprotein cholesterol (standardized mean difference 0.22, 95% confidence interval 0.04-0.41; P = 0.02) and decrease in triglyceride (standardized mean difference -0.19; 95% confidence interval -0.37 to 0.02; P = 0.03) than that in control diets. CONCLUSIONS: Our findings suggest efficacy of long-term LCD in treating dyslipidemia in individuals with type 2 diabetes, but do not recommend long-term LCD for glycemic control in the individuals.
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BACKGROUND: Systemic edema is an adverse effect of docetaxel chemotherapy and causes distress to patients, including those receiving this agent for breast cancer. However, its characteristics and factors related to its effect on quality of life (QoL) have not been adequately investigated. In this study, we assessed systemic edema quantitatively, explored related factors, and evaluated QoL in patients receiving docetaxel for breast cancer. METHODS: The study had a prospective cohort design and included 37 patients with no known history of swelling who were treated with docetaxel between September 2019 and April 2022. Patients were examined at the start, middle, and end of their course of treatment and 1 and 2 months later. Body water content, body mass, fat mass, and muscle mass were quantified using bioelectrical impedance analysis. Systemic edema was evaluated with reference to the Common Terminology Criteria for Adverse Events. The timing of development of systemic edema at any anatomical site that was grade 2 or worse was recorded. QoL was assessed using the Quality of Life-Anti Cancer Drug scale. Nutrition was evaluated using the Brief-type self-administered diet history questionnaire. Multivariable logistic regression analysis was performed to identify related factors. QoL was also compared between patients with edema and those without edema. RESULTS: Systemic edema developed in 67% of the study participants and was most prevalent at the end of treatment. Body fat mass (adjusted odds ratio [aOR] 0.802, 95% confidence interval [CI] 0.651-0.988, p = 0.038), disease stage (aOR 3.279, 95% CI 0.493-21.793, p = 0.219), and history of alcohol consumption (aOR 0.141, 95% CI 0.013-1.521, p = 0.106) were identified as risk factors for docetaxel-induced edema. Participants who developed systemic edema experienced more physical, vital, and emotional distress 1 month after treatment than those who did not. There was no association between systemic edema and nutrition. CONCLUSIONS: Systemic edema may develop after treatment with docetaxel and increase distress in patients with a high body fat mass. Patients at risk of systemic edema should be informed in advance about the potential frequency, location, and timing of its onset and encouraged to self-manage this condition.