利格列汀治疗2型糖尿病重度肾脏损伤患者有效性和安全性的临床应用

Efficacy and safety of linagliptin in patients with type 2 diabetes and severe renal impairment

目的:观察DPP-4抑制剂利格列汀治疗2型糖尿病重度肾脏损伤患者的有效性和安全性。方法:84例2型糖尿病(HbA1c7.0%～10.0%)合并严重肾脏损伤(eGFR<30mL·min^(-1)·1.73m^(-2))患者,在原有降糖药物基础上,按1∶1比例随机分为利格列汀组(5mg每日一次口服)(n=41)和安慰剂组(n=43)。主要有效终点是12周后HbA1c自基线的变化。结果:12周后,利格列汀组HbA1c下降0.71%,而安慰剂组下降0.12%(P<0.000 1)。利格列汀组与安慰剂相比,1,5脱水葡萄糖醇明显升高(36.4±12.3)ng·mL^(-1) vs.(10.4±5.2)ng·mL^(-1),P<0.05)。两组总的不良反应类似(35%vs.32.5%),严重低血糖反应率都较低(每组2例)。利格列汀和安慰剂对肾功能影响较小(eGFR下降,0.8mL·min^(-1)·1.73m^(-2) vs.2mL·min^(-1)·1.73m^(-2)),没有药物相关的肾衰竭发生。结论:利格列汀治疗2型糖尿病严重肾脏损伤患者,有效地降低血糖,严重低血糖发生少,且没有影响肾功能、引起药物相关的肾衰,是可以用于治疗2型糖尿病重度肾脏损伤患者的降糖药物。

OBJECTIVE To observe efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in patients with type 2 diabetes and severe renal impairment (RI).METHODS Eighty-four patients with type 2 diabetes (HbA1c 7.0%-10.0%) and severe RI (estimated glomerular filtration rate (eGFR) <30 mL·min^-1·1.73 m^-2) were randomized to receive linagliptin 5 mg (n=41) or placebo (n=43) once daily based on the existing background therapy.The primary efficacy endpoint was HbA1c change from baseline to week 12.RESULTS At week 12,adjusted mean HbA1c decreased by 0.71% with linagliptin and 0.12% with placebo (P<0.000 1).Linagliptin group showed a significant increase in 1,5-anhydroglucitol compared with placebo (36.4±12.3) ng·mL^-1 vs.(10.4±5.2) ng·mL^-1,P<0.05).Overall adverse event incidence was similar (35% vs. 32.5%).Incidence of severe hypoglycemia with linagliptin and placebo was comparably low (two patients per group).Linagliptin and placebo had little effect on renal function (median change in eGFR,-0.8 mL·min^-1·1.73 m^-2 vs. -2 mL·min^-1·1.73 m^-2),and no drug related renal failure occurred.CONCLUSION In patients with type 2 diabetes and severe RI,linagliptin provides clinically meaningful improvements in glycemic control with very low risk of severe hypoglycemia,and no case of drug-related renal failure.