The Ohio State University, Dublin, OH 43016, USA.
Postgrad Med. 2013 May;125(3):21-32. doi: 10.3810/pgm.2013.05.2654.
Clinical development programs of investigational antidiabetic agents now include evaluation of cardiovascular (CV) risk as a major research focus. Recently, several compounds in a new class of antihyperglycemic therapy have reached the final stages of development. Treatment with inhibitors of sodium-glucose co-transporters 2 (SGLT2) leads to urinary excretion of glucose in patients with type 2 diabetes mellitus (T2DM), and is associated with clinically significant reductions in blood glucose levels. The glucosuria-based mechanism of this class has the potential to induce weight loss through reduced caloric availability, and, in addition, may affect blood pressure (BP) via osmotic diuresis or other as yet incompletely characterized mechanisms.
Searches of the PubMed database were conducted for published studies evaluating the use of SGLT2 inhibitors that reported data on CV risk factors (eg, weight, BP, lipid levels) or CV events. Searches for presentations at recent major diabetes congresses were performed using the Online Submission and Invitation System.
Treatment with SGLT2 inhibitors has consistently been associated with reduction in body weight and BP. Qualitative graphical assessment of 21 studies shows unadjusted reductions in systolic BP and body weight typically ranging between 3 to 5 mm Hg and 2 to 3 kg, respectively. A few reports have suggested the potential for improvement in lipid parameters, such as high-density lipoprotein cholesterol levels; however, not all studies have demonstrated significant changes, and some have noted small increases in low-density lipoprotein cholesterol levels.
Inhibition of SGLT2 in patients with T2DM may be associated with significant weight loss and BP reduction that are sustainable over the average time span of an investigational clinical study (ie, 3-6 months). When considered in terms of the potential for combination therapy, these features may offer a means of further reducing metabolic and CV risk in patients with T2DM.
目前，研究性抗糖尿病药物的临床开发项目将心血管（CV）风险评估作为主要研究重点。最近，一类新型抗高血糖治疗药物的几种化合物已进入开发的最后阶段。钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂的治疗可导致 2 型糖尿病（T2DM）患者的葡萄糖尿排泄，与血糖水平的显著降低相关。该类药物基于葡萄糖尿的机制，通过减少热量供应，有可能导致体重减轻，此外，通过渗透性利尿或其他尚未完全确定的机制，可能影响血压（BP）。
在 PubMed 数据库中进行了发表的评估 SGLT2 抑制剂使用的研究的检索，这些研究报告了 CV 危险因素（如体重、BP、血脂水平）或 CV 事件的数据。使用在线提交和邀请系统对最近的主要糖尿病大会的演示文稿进行了搜索。
SGLT2 抑制剂的治疗一直与体重和 BP 的降低相关。对 21 项研究的定性图形评估显示，未调整的收缩压和体重通常分别降低 3 至 5 mmHg 和 2 至 3 kg。一些报告表明，血脂参数（如高密度脂蛋白胆固醇水平）可能有所改善；然而，并非所有研究都表明有显著变化，有些研究注意到低密度脂蛋白胆固醇水平略有增加。
在 T2DM 患者中抑制 SGLT2 可能与体重显著减轻和 BP 降低相关，在研究性临床研究的平均时间范围内（即 3-6 个月）可持续。考虑到联合治疗的潜力，这些特征可能为进一步降低 T2DM 患者的代谢和 CV 风险提供一种方法。
