Department of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine, Niigata, Japan.
Clinical Data Science Department, Kowa Co., Ltd., Tokyo, Japan.
Diabet Med. 2020 Aug;37(8):1316-1325. doi: 10.1111/dme.14279. Epub 2020 Mar 17.
To examine the effects of a sodium-glucose co-transporter 2 (SGLT2) inhibitor, tofogliflozin, on resting heart rate by exploring baseline factors that independently influenced changes in the resting heart rate.
Data on 419 participants in tofogliflozin phase 2/3 trials were analysed. Changes in resting heart rate from baseline to week 24 were analysed using an analysis of covariance (ANCOVA) model with groups (tofogliflozin/placebo) as a fixed effect and baseline values as covariates. The antilipolytic effect was evaluated as adipose tissue insulin resistance (Adipo-IR) and was calculated as the product of fasting insulin and free fatty acid. Multivariate analysis evaluated independent factors for changes in resting heart rate from baseline to week 24.
Of the participants, 58% were men, and mean age, HbA , BMI and resting heart rate were 57.6 years, 65 mmol/mol (8.1%), 25.5 kg/m and 66 bpm, respectively. At week 24, adjusted mean difference vs. placebo in the change from baseline was -2.3 bpm [95% confidence interval (CI) -4.6, -0.1] with tofogliflozin. Changes in resting heart rate were positively correlated with changes in Adipo-IR, whereas reductions in HbA , body weight and blood pressure were similar independent of changes in resting heart among quartiles of resting heart rate change. On multivariate analysis, higher baseline resting heart rates and Adipo-IR values were significantly associated with greater reductions in resting heart rate.
Tofogliflozin corrected resting heart rate levels in accordance with baseline levels. Correction of high resting heart rates may be attributed to improved adipose tissue insulin resistance, leading to correction of hyperinsulinaemia.
通过探讨独立影响静息心率变化的基线因素，研究钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂托格列净对静息心率的影响。
对托格列净 2/3 期临床试验的 419 名参与者的数据进行分析。采用协方差分析（ANCOVA）模型，以组（托格列净/安慰剂）为固定效应，以基线值为协变量，分析从基线到 24 周静息心率的变化。抗脂肪分解作用评估为脂肪组织胰岛素抵抗（Adipo-IR），计算公式为空腹胰岛素与游离脂肪酸的乘积。多元分析评估了从基线到 24 周静息心率变化的独立因素。
参与者中 58%为男性，平均年龄、HbA1c、BMI 和静息心率分别为 57.6 岁、65mmol/mol（8.1%）、25.5kg/m²和 66bpm。在 24 周时，与安慰剂相比，托格列净组从基线到 24 周的调整平均差值为-2.3bpm[95%置信区间（CI）为-4.6，-0.1]。静息心率的变化与 Adipo-IR 的变化呈正相关，而 HbA1c、体重和血压的降低与静息心率变化的 quartiles 中静息心率的降低无关。多元分析显示，较高的基线静息心率和 Adipo-IR 值与静息心率降低幅度较大显著相关。
托格列净可根据基线水平校正静息心率。静息心率的校正可能归因于改善的脂肪组织胰岛素抵抗，从而纠正高胰岛素血症。
