Saulsberry W J, Coleman C I, Mearns E S, Zaccaro E, Doleh Y, Sobieraj D M
Department of Pharmacy Practice, School of Pharmacy, University of Connecticut, Storrs, CT, USA.
Int J Clin Pract. 2015 Nov;69(11):1221-35. doi: 10.1111/ijcp.12698. Epub 2015 Jul 28.
Determine the efficacy and safety of antidiabetic agents added-on to metformin and a thiazolidinedione (TZD) in patients with inadequately controlled type 2 diabetes (T2D).
MEDLINE and CENTRAL were searched for randomised controlled trials (RCTs) evaluating the addition of an antidiabetic agent in patients with T2D inadequately controlled on stable, optimised metformin and TZD therapy (≥ 1500 mg metformin and ≥ 50% maximum TZD dose for ≥ 4 weeks). Frequentist network meta-analysis was performed on identified studies.
Eleven RCTs evaluating dipeptidyl peptidase-4 inhibitors (linagliptin, sitagliptin), sulfonylureas (SUs) (glibenclamide, glimepiride), glucagon-like peptide-1 (GLP-1) analogues (exenatide, liraglutide, dulaglutide, taspoglutide) and sodium-glucose cotransporter2 (SGLT2) inhibitors (canagliflozin, empagliflozin) were identified. The mean reduction in HbA1c from baseline was significant for all agents (range, 0.55-1.17%) vs. placebo. SUs were associated with weight gain (range, 3.31-7.29 kg), while weight loss was seen with all GLP-1 analogues (range, 1.53-2.20 kg) and SGLT2 inhibitors (range, 2.08-2.95 kg) vs. placebo. Relative risk of hypoglycaemia was increased with dulaglutide, exenatide and glimepiride vs. placebo (RR range, 2.65-6.17); and trended higher with all other agents except linagliptin. GLP-1 analogues and canagliflozin reduced systolic blood pressure vs. placebo (range, 2.39-5.05 mmHg). No agent with available data increased the risk of urinary or genital tract infection vs. placebo.
When added to stable, optimised metformin and TZD, all evaluated antidiabetic agents reduced HbA1c; albeit not to the same degree. Moreover, agents differed in their effects on body weight, hypoglycaemia and systolic blood pressure.
确定在二甲双胍和噻唑烷二酮类药物（TZD）基础上加用抗糖尿病药物对2型糖尿病（T2D）控制不佳患者的疗效和安全性。
检索MEDLINE和CENTRAL数据库，查找评估在接受稳定、优化的二甲双胍和TZD治疗（≥1500 mg二甲双胍且≥50%最大TZD剂量，持续≥4周）但血糖控制不佳的T2D患者中加用抗糖尿病药物的随机对照试验（RCT）。对纳入的研究进行频率学派网状Meta分析。
共识别出11项评估二肽基肽酶-4抑制剂（利格列汀、西他列汀）、磺脲类药物（SUs）（格列本脲、格列美脲）、胰高血糖素样肽-1（GLP-1）类似物（艾塞那肽、利拉鲁肽、度拉鲁肽、塔司鲁肽）和钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂（卡格列净、恩格列净）的RCT。与安慰剂相比，所有药物的糖化血红蛋白（HbA1c）从基线水平的平均降幅均显著（范围为0.55 - 1.17%）。SUs与体重增加相关（范围为3.31 - 7.29 kg），而与安慰剂相比，所有GLP-1类似物（范围为1.53 - 2.20 kg）和SGLT2抑制剂（范围为2.08 - 2.95 kg）均出现体重减轻。与安慰剂相比，度拉鲁肽、艾塞那肽和格列美脲的低血糖相对风险增加（相对风险范围为2.65 - 6.17）；除利格列汀外，所有其他药物的低血糖相对风险均呈上升趋势。与安慰剂相比，GLP-1类似物和卡格列净可降低收缩压（范围为2.39 - 5.05 mmHg）。与安慰剂相比，没有一种有可用数据的药物会增加泌尿系统或生殖道感染的风险。
在稳定、优化的二甲双胍和TZD基础上加用抗糖尿病药物时，所有评估的抗糖尿病药物均可降低HbA1c，尽管程度不同。此外，这些药物在对体重、低血糖和收缩压的影响方面存在差异。
