Lingvay Ildiko
Endocr Pract. 2017 Jul;23(7):831-840. doi: 10.4158/EP161725.RA. Epub 2017 Mar 23.
This article reviews evidence supporting sodium glucose cotransporter 2 (SGLT2) inhibitor and dipeptidyl peptidase-4 (DPP-4) inhibitor combination therapy for management of type 2 diabetes mellitus (T2DM).
We conducted a nonsystematic review of the literature focusing on single-pill or fixed-dose combinations of SGLT2 inhibitors and DPP-4 inhibitors available in the United States.
SGLT2 inhibitors and DPP-4 inhibitors have complementary mechanisms of action that address several of the underlying pathophysiologic abnormalities present in T2DM without overlapping toxicities. The combination of these 2 agents has several advantages including a low risk of hypoglycemia, the potential for weight loss, the ability to coformulate into a pill with once-daily administration, and the possibility to use with other classes of glucose-lowering agents. Cardiovascular outcomes trials reported to date support the safety of the DPP-4 class and suggest possible cardioprotective effects for SGLT2 inhibitors - at least based on the first reported study that used empagliflozin. Recent clinical evidence shows that SGLT2 inhibitor/DPP-4 inhibitor therapy is an effective combination for T2DM treatment, providing glycated hemoglobin (HbA1c) reductions of 1.1 to 1.5%, and weight reductions of approximately 2 kg when added to metformin, which is its primary place in therapy.
The combination of an SGLT2 inhibitor/DPP-4 inhibitor is a safe and effective treatment choice for patients with T2DM who are unable to obtain adequate glycemic control with metformin therapy, cannot use metformin, or have a higher baseline HbA1c.
BP = blood pressure; CI = confidence interval; CVOT = cardiovascular outcomes; DKA = diabetic ketoacidosis; DPP-4 = dipeptidyl peptidase-4; EXAMINE = EXamination of cArdiovascular outcoMes with alogliptiN versus standard of carE in patients with type 2 diabetes mellitus and acute coronary syndrome; FDA = Food and Drug Administration; HbA1c = glycated hemoglobin; HR = hazard ratio; MACE = major adverse cardiovascular events; SAVOR-TIMI 53 = Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Type 2 Diabetes Mellitus; SBP = systolic blood pressure; SGLT2 = sodium glucose cotransporter 2; TECOS = Trial to Evaluate Cardiovascular Outcomes after Treatment with Sitagliptin; T2DM = type 2 diabetes mellitus; XR = extended release.
本文综述了支持钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂与二肽基肽酶-4（DPP-4）抑制剂联合治疗2型糖尿病（T2DM）的证据。
我们对文献进行了非系统性综述，重点关注美国可用的SGLT2抑制剂与DPP-4抑制剂的单片或固定剂量组合。
SGLT2抑制剂和DPP-4抑制剂具有互补的作用机制，可解决T2DM中存在的几种潜在病理生理异常，且无重叠毒性。这两种药物联合使用有几个优点，包括低血糖风险低、有减重潜力、能够制成每日一次给药的单片制剂，以及可与其他降糖药物联合使用。迄今为止报道的心血管结局试验支持DPP-4类药物的安全性，并提示SGLT2抑制剂可能具有心脏保护作用——至少基于首次报道的使用恩格列净的研究。最近的临床证据表明，SGLT2抑制剂/DPP-4抑制剂疗法是治疗T2DM的有效联合方案，在加用二甲双胍（其主要治疗地位）时，糖化血红蛋白（HbA1c）降低1.1%至1.5%，体重减轻约2 kg。
对于无法通过二甲双胍治疗获得充分血糖控制、不能使用二甲双胍或基线HbA1c较高的T2DM患者，SGLT2抑制剂/DPP-4抑制剂联合治疗是一种安全有效的治疗选择。
BP = 血压；CI = 置信区间；CVOT = 心血管结局；DKA = 糖尿病酮症酸中毒；DPP-4 = 二肽基肽酶-4；EXAMINE = 2型糖尿病和急性冠状动脉综合征患者中阿格列汀与标准治疗的心血管结局研究；FDA = 美国食品药品监督管理局；HbA1c = 糖化血红蛋白；HR = 风险比；MACE = 主要不良心血管事件；SAVOR-TIMI 53 = 2型糖尿病患者中沙格列汀血管结局评估记录；SBP = 收缩压；SGLT2 = 钠-葡萄糖协同转运蛋白2；TECOS = 西他列汀治疗后心血管结局评估试验；T2DM = 2型糖尿病；XR = 缓释
