Takasu Toshiyuki, Hayashizaki Yuka, Hirosumi Jiro, Minoura Hideaki, Amino Nobuaki, Kurosaki Eiji, Takakura Shoji
Tsukuba Research Center, Drug Discovery Research, Astellas Pharma Inc.
Biol Pharm Bull. 2017;40(5):675-680. doi: 10.1248/bpb.b16-00964.
Sodium glucose cotransporter 2 (SGLT2) inhibitors improve hyperglycemia in patients with type 2 diabetes mellitus (T2DM) by increasing urinary glucose excretion. In addition to their antihyperglycemic effect, SGLT2 inhibitors also reduce body weight and fat mass in obese and overweight patients with T2DM. However, whether or not SGLT2 inhibitors similarly affect body composition of non-obese patients with T2DM remains unclear. In this study, we investigated the effect of the SGLT2 inhibitor ipragliflozin on body composition in a Goto-Kakizaki (GK) rat model of non-obese T2DM. GK rats were treated with ipragliflozin once daily for 9 weeks, starting at 23 weeks of age. Body composition was then analyzed using dual-energy X-ray absorptiometry. Treatment with ipragliflozin increased urinary glucose excretion, reduced hemoglobin A1c (HbA1c) levels and suppressed body weight gain as the dose increased. Body composition analysis revealed that body fat mass was lower in the ipragliflozin-treated groups than in the control group, while lean body mass and bone mineral contents were comparable between groups. Thus, an SGLT2 inhibitor ipragliflozin was found to promote preferential loss of fat mass in a rat model of non-obese T2DM. Ipragliflozin might also promote preferential loss of fat in non-obese patients with T2DM.
钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂通过增加尿糖排泄来改善2型糖尿病（T2DM）患者的高血糖状况。除了具有抗高血糖作用外，SGLT2抑制剂还能降低肥胖和超重的T2DM患者的体重和脂肪量。然而，SGLT2抑制剂是否同样会影响非肥胖T2DM患者的身体组成仍不清楚。在本研究中，我们在非肥胖T2DM的Goto-Kakizaki（GK）大鼠模型中研究了SGLT2抑制剂依帕列净对身体组成的影响。从23周龄开始，GK大鼠每天接受一次依帕列净治疗，持续9周。然后使用双能X线吸收法分析身体组成。依帕列净治疗可增加尿糖排泄，降低糖化血红蛋白（HbA1c）水平，并随着剂量增加抑制体重增加。身体组成分析显示，依帕列净治疗组的体脂肪量低于对照组，而两组之间的去脂体重和骨矿物质含量相当。因此，在非肥胖T2DM大鼠模型中发现SGLT2抑制剂依帕列净可促进脂肪量的优先减少。依帕列净也可能促进非肥胖T2DM患者优先减少脂肪。
