Kutoh Eiji, Wada Asuka, Kuto Alexandra N, Hayashi Jyunka, Kurihara Rumi
Division of Clinical Research, Biomedical Center , Tokyo, Japan.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Gyoda General Hospital , Saitama, Japan.
Hosp Pract (1995). 2020 Mar 14;48(2):68-74. doi: 10.1080/21548331.2020.1732098. Epub 2020 Mar 3.
The aim of this study is to investigate the correlations between the changes of body weight and metabolic parameters during canagliflozin treatment.
Drug naïve subjects with T2DM (n = 84) received canagliflozin monotherapy for 3 months. The subjects were divided into three groups with equal numbers of subjects (n = 28 each) according to the reductions of BMI levels; highest (group A), intermediate (group B), and lowest (group C) reductions. Changes of the metabolic parameters were compared between group A and group C. These two groups acted as a control of each other.
Significant reductions of BMI levels (-4.1%, p < 0.00001) were observed in group A, while, surprisingly, significant increases (+1.5%, p < 0.00001) were seen in group C. In these two groups, similar reductions of HbA1c, FBG, or HOMA-R, and increases of HOMA-B levels were observed. Significant reductions of TG levels (-18.6%) were seen only in group A. At baseline, HbA1c levels were significantly lower in group A versus group C (p < 0.03). In group A, significant correlations between the changes of BMI and those of HbA1c (R = 0.496) were seen. By contrast, in group C, significant negative correlations were observed between these parameters (R = -0.463).
These results suggest that certain populations treated with canagliflozin gained weight, though similar glycemic and beta-cell/insulin sensitivity enhancing properties were observed in comparison to those with efficient weight reductions. Those who lost more weight had better glycemic efficacy in group A. By contrast, those who gained more weight had better glycemic efficacy in group C. Distinct glucose-lowering mechanisms might be operating between these two groups. Involvement of some factors including glucagons and free fatty acids is hypothesized.
本研究旨在探讨卡格列净治疗期间体重变化与代谢参数之间的相关性。
初治的2型糖尿病患者（n = 84）接受卡格列净单药治疗3个月。根据体重指数（BMI）水平降低程度将受试者分为三组，每组人数相等（每组n = 28）；降低程度最高组（A组）、中等降低程度组（B组）和降低程度最低组（C组）。比较A组和C组代谢参数的变化。这两组互为对照。
A组BMI水平显著降低（-4.1%，p < 0.00001），而令人惊讶的是，C组BMI水平显著升高（+1.5%，p < 0.00001）。在这两组中，糖化血红蛋白（HbA1c）、空腹血糖（FBG）或胰岛素抵抗指数（HOMA-R）均有类似程度的降低，而胰岛β细胞功能指数（HOMA-B）水平升高。仅A组甘油三酯（TG）水平显著降低（-18.6%）。基线时，A组HbA1c水平显著低于C组（p < 0.03）。在A组中，BMI变化与HbA1c变化之间存在显著相关性（R = 0.496）。相比之下，在C组中，这些参数之间存在显著负相关（R = -0.463）。
这些结果表明，接受卡格列净治疗的某些人群体重增加，尽管与体重有效降低的人群相比，观察到类似的血糖和β细胞/胰岛素敏感性增强特性。在A组中，体重减轻更多的患者血糖疗效更好。相比之下，在C组中，体重增加更多的患者血糖疗效更好。这两组可能存在不同的降糖机制。推测一些因素包括胰高血糖素和游离脂肪酸参与其中。
