Sakai Soichi, Kaku Kohei, Seino Yutaka, Inagaki Nobuya, Haneda Masakazu, Sasaki Takashi, Fukatsu Atsushi, Kakiuchi Haruka, Samukawa Yoshishige
Taisho Pharmaceutical Co., Ltd., Tokyo, Japan.
Department of Internal Medicine, Kawasaki Medical School, Okayama, Japan.
Clin Ther. 2016 Apr;38(4):843-862.e9. doi: 10.1016/j.clinthera.2016.01.017. Epub 2016 Mar 25.
Luseogliflozin, a sodium-glucose cotransporter-2 inhibitor, may be beneficial in obese diabetic patients based on its potential to decrease blood glucose and body weight, but there is limited proof. This analysis aimed to investigate the efficacy and safety of luseogliflozin in patients with varying levels of obesity.
A pooled analysis of four 52-week Phase III trials of luseogliflozin 2.5 mg daily (or up to 5 mg daily) in Japanese patients with type 2 diabetes mellitus stratified according to baseline body mass index (BMI) was conducted. Efficacy end points included changes in glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), and body weight.
In total, 1031 patients were included and stratified into 5 BMI (kg/m(2)) groups: low-to-medium (<22.5, n = 222); medium (≥22.5 to <25, n = 270); high-level 1 (≥25 to <27.5, n = 262); high-level 2 (≥27.5 to <30, n = 142); and very-high (≥30, n = 135). HbA1c decreased significantly compared with baseline until week 52 in all groups, and a similar trend was observed with FPG and body weight. The reduction in glycemic parameters tended to be slightly smaller in patients with BMI <22.5 kg/m(2), and the reduction in body weight tended to be greater in patients with higher BMI, especially those with BMI ≥30 kg/m(2). Levels of fasting insulin, C-peptide immunoreactivity, triglyceride, blood pressure, aspartate aminotransferase, alanine aminotransferase, and uric acid decreased significantly at week 52 in all groups (except for aspartate aminotransferase in patients with BMI <22.5 kg/m(2)). Levels of these parameters tended to be higher at baseline and these enhanced levels resulted in a greater decrease in patients with higher BMI. In safety, the incidence of adverse events was similar between groups, and most of them were mild in severity.
HbA1c and body weight decreased significantly in all groups. Decrease in glycemic parameters tended to be smaller in patients with BMI <22.5 kg/m(2), while that of body weight was larger in patients with higher BMI. Furthermore, luseogliflozin was especially beneficial in patients with higher BMI in terms of metabolic abnormalities, including insulin secretion and hypertension. Luseogliflozin exhibited a favorable and similar safety profile over 52 weeks in all groups. This agent can be an effective and well-tolerated therapeutic option in patients with a wide range of BMI levels, and it may be more beneficial in patients with higher BMI.
鲁格列净是一种钠-葡萄糖协同转运蛋白2抑制剂，因其具有降低血糖和体重的潜力，可能对肥胖糖尿病患者有益，但相关证据有限。本分析旨在研究鲁格列净在不同肥胖程度患者中的疗效和安全性。
对四项为期52周的Ⅲ期试验进行汇总分析，这些试验针对日本2型糖尿病患者，每日服用2.5毫克鲁格列净（或每日最高5毫克），并根据基线体重指数（BMI）进行分层。疗效终点包括糖化血红蛋白（HbA1c）、空腹血糖（FPG）和体重的变化。
总共纳入了1031名患者，并将其分为5个BMI（kg/m²）组：低至中等（<22.5，n = 222）；中等（≥22.5至<25，n = 270）；高水平1（≥25至<27.5，n = 262）；高水平2（≥27.5至<30，n = 142）；以及非常高（≥30，n = 135）。与基线相比，所有组在第52周时HbA1c均显著下降，FPG和体重也呈现类似趋势。BMI<22.5 kg/m²的患者血糖参数下降幅度往往略小，而BMI较高的患者体重下降幅度往往更大，尤其是BMI≥30 kg/m²的患者。所有组在第52周时空腹胰岛素、C肽免疫反应性、甘油三酯、血压、天冬氨酸转氨酶、丙氨酸转氨酶和尿酸水平均显著下降（BMI<22.5 kg/m²的患者中天冬氨酸转氨酶除外）。这些参数在基线时往往较高，且较高的基线水平导致BMI较高的患者下降幅度更大。在安全性方面，各组不良事件发生率相似，且大多数为轻度。
所有组的HbA1c和体重均显著下降。BMI<22.5 kg/m²的患者血糖参数下降幅度往往较小，而BMI较高的患者体重下降幅度较大。此外，鲁格列净在包括胰岛素分泌和高血压在内的代谢异常方面，对BMI较高的患者尤其有益。在所有组中，鲁格列净在52周内表现出良好且相似的安全性。该药物对于广泛BMI水平的患者可能是一种有效且耐受性良好的治疗选择，对BMI较高的患者可能更有益。
