恩格列净与利格列汀联合治疗2型糖尿病患者

Empagliflozin and linagliptin combination therapy for treatment of patients with type 2 diabetes mellitus.

作者信息

Triplitt C, Solis-Herrera C, Cersosimo E, Abdul-Ghani M, Defronzo Ralph A

机构信息

a Department of Medicine, Diabetes Division , University of Texas Health Science Center and Texas Diabetes Institute , San Antonio , TX 78229 , USA.

出版信息

Expert Opin Pharmacother. 2015;16(18):2819-33. doi: 10.1517/14656566.2015.1114098. Epub 2015 Nov 19.

DOI:10.1517/14656566.2015.1114098

PMID:26583910

Abstract

INTRODUCTION

Many patients with type 2 diabetes mellitus (T2DM) fail to achieve the desired A1c goal because the antidiabetic medications used do not correct the underlying pathophysiologic abnormalities and monotherapy is not sufficiently potent to reduce the A1c to the 6.5 - 7.0% range. Insulin resistance and islet (beta and alpha) cell dysfunction are major pathophysiologic abnormalities in T2DM. We examine combination therapy with linagliptin plus empagliflozin as a therapeutic approach for the treatment of inadequately controlled T2DM patients.

AREAS COVERED

A literature search of all human diabetes, metabolism and general medicine journals from year 2000 to the present was conducted. Glucagon like peptide-1 (GLP-1) deficiency/resistance contributes to islet cell dysfunction by impairing insulin secretion and increasing glucagon secretion. DPP-4 inhibitors (DPP4i) improve pancreatic islet function by augmenting glucose-dependent insulin secretion and decreasing elevated plasma glucagon levels. Linagliptin, a DPP-4 inhibitor, reduces HbA1c, is weight neutral, has an excellent safety profile and a low risk of hypoglycemia. The expression of sodium-glucose cotransporter-2 (SGLT2) in the proximal renal tubule is upregulated in T2DM, causing excess reabsorption of filtered glucose. The SGLT2 inhibitor (SGLT2i), empagliflozin, improves HbA1c by causing glucosuria and ameliorating glucotoxicity. It also decreases weight and blood pressure, and has a low risk of hypoglycemia.

EXPERT OPINION

The once daily oral combination of linagliptin plus empagliflozin does not increase the risk of hypoglycemia and tolerability and discontinuation rates are similar to those with each as monotherapy. At HbA1c values below 8.5% linagliptin/empagliflozin treatment produces an additive effect, whereas above 8.5%, there is a less than additive reduction with combination therapy compared with the effect of each agent alone. Linagliptin/empagliflozin addition is a logical combination in patients with T2DM, especially those with an HbA1c < 8.5%.

摘要

引言

许多2型糖尿病（T2DM）患者未能达到理想的糖化血红蛋白（A1c）目标，原因在于所使用的抗糖尿病药物无法纠正潜在的病理生理异常，且单一疗法的效力不足以将A1c降至6.5 - 7.0%的范围。胰岛素抵抗和胰岛（β细胞和α细胞）功能障碍是T2DM的主要病理生理异常。我们研究了利那格列汀联合恩格列净的联合疗法，作为治疗控制不佳的T2DM患者的一种治疗方法。

涵盖领域

对2000年至今的所有人类糖尿病、代谢和普通医学期刊进行了文献检索。胰高血糖素样肽-1（GLP-1）缺乏/抵抗通过损害胰岛素分泌和增加胰高血糖素分泌导致胰岛细胞功能障碍。二肽基肽酶-4抑制剂（DPP4i）通过增强葡萄糖依赖性胰岛素分泌和降低升高的血浆胰高血糖素水平来改善胰岛功能。利那格列汀是一种DPP-4抑制剂，可降低糖化血红蛋白（HbA1c），对体重无影响，具有良好的安全性和低血糖风险。T2DM患者近端肾小管中钠-葡萄糖协同转运蛋白-2（SGLT2）的表达上调，导致滤过葡萄糖的过度重吸收。SGLT2抑制剂（SGLT2i）恩格列净通过导致糖尿和改善糖毒性来改善HbA1c。它还可减轻体重和降低血压，且低血糖风险较低。

专家意见

利那格列汀联合恩格列净每日一次口服不会增加低血糖风险，耐受性和停药率与单一疗法相似。在HbA1c值低于8.5%时，利那格列汀/恩格列净治疗产生相加效应，而在高于8.5%时，与单独使用每种药物的效果相比，联合疗法的降低效果小于相加效应。对于T2DM患者，尤其是HbA1c < 8.5%的患者，添加利那格列汀/恩格列净是一种合理的联合用药。