DPP-4抑制剂在2型糖尿病治疗中的临床地位评价
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摘要
近年来,越来越多的临床研究证实DPP-4抑制剂疗效确切,低血糖风险小、体重影响中性、安全性和耐受性良好。国内外多个糖尿病诊治指南已将该类药物列入临床治疗路径。目前,国内已上市5种DPP-4抑制剂有:西格列汀、维格列汀、沙格列汀、利格列汀和阿格列汀。本文重点阐述了DPP-4抑制剂降糖疗效、心血管安全性、不良反应等的中国证据和最新国外进展,总结了其在2型糖尿病人群,包括老年、肝肾功能不全等特殊人群中的临床应用证据。
Recently, more and more clinical studies have confirmed that DPP-4 inhibitors have a definite therapeutic effect with a low risk of hypoglycemia, neutral effect on weight and good tolerance. Most of international guidelines and our Chinese Diabetes Society guideline for the treatment of type 2 diabetes have included this class of drugs in their updated versions. Five DPP-4 inhibitors, including sitagliptin, vildagliptin,saxagliptin, linagliptin and alogliptin have been launched in China since 2010. This article aims to review the Chinese evidence and foreign progress of DPP-4 inhibitors on hypoglycemic efficacy, cardiovascular safety, adverse effects, etc. and summarize the application of DPP-4 inhibitors in type 2 diabetes including special populations such as the elderly patients and those with liver and kidney dysfunction.
Recently, more and more clinical studies have confirmed that DPP-4 inhibitors have a definite therapeutic effect with a low risk of hypoglycemia, neutral effect on weight and good tolerance. Most of international guidelines and our Chinese Diabetes Society guideline for the treatment of type 2 diabetes have included this class of drugs in their updated versions. Five DPP-4 inhibitors, including sitagliptin, vildagliptin,saxagliptin, linagliptin and alogliptin have been launched in China since 2010. This article aims to review the Chinese evidence and foreign progress of DPP-4 inhibitors on hypoglycemic efficacy, cardiovascular safety, adverse effects, etc. and summarize the application of DPP-4 inhibitors in type 2 diabetes including special populations such as the elderly patients and those with liver and kidney dysfunction.
引文
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[3] Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on The Comprehensive Type 2 Diabetes Management Algorithm--2016 Executive Summary[J]. Endocr Pract, 2016, 22(1):84-113.
[4]中国老年学会老年医学会老年内分泌代谢专员委员会.老年糖尿病诊疗措施专家共识(2013年版)[J].中华内科杂志,2014, 53:243-251.
[5]中华医学会内分泌学分会,中国药学会医院药学专业委员会.基于肠促胰素治疗药物临床应用的快速建议指南[J].中华内分泌代谢杂志,2016,32(6):448-454.
[6] Mohan V, Yang W, Son HY, et al. Efficacy and safety of sitagliptin in the treatment of patients with type 2 diabetes in China, India, and Korea[J].Diabetes Res Clin Pract,2009, 83(1):106-116.
[7] Wu W, Li Y, Chen X, et al. Effect of Linagliptin on Glycemic Control in Chinese Patients with Newly-Diagnosed, Drug-Naive Type 2 Diabetes Mellitus:A Randomized Controlled Trial[J]. Med Sci Monit, 2015,21:2678-2684.
[8] Cai X, Han X, Luo Y, et al. Efficacy of dipeptidyl-peptidase-4 inhibitors and impact on p-cell function in Asian and Caucasian type 2 diabetes mellitus patients:A meta-analysis[J]. J Diabetes, 2015, 7(3):347-359.
[9] Pan C, Yang W, Barona JP, et al. Comparison of vildagliptin and acarbose monotherapy in patients with Type 2 diabetes:a 24-week, double-blind,randomized trial[J]. Diabet Med, 2008, 25(4):435-441.
[10]靳淇,陈海燕,孔俭,等.DPP-4抑制剂西格列汀对2型糖尿病患者的治疗作用[J].中国老年学杂志,2013, 33(17):4105-4106.
[11]叶潇,张倩,曹瑛,等.西格列汀与阿卡波糖治疗新诊断2型糖尿病患者的疗效比较[J].中国糖尿病杂志,2012, 20(8):619-621.
[12] Cai X, Yang W, Zhou L, et al. Comparisons of the efficacy of glucose control,lipid profile, andβ-cell function between DPP-4 inhibitors and AGI treatment in type 2 diabetes patients:a meta-analysis[J]. Endocrine, 2015, 50(3):590-597.
[13] Yang W, Guan Y, Shentu Y, et al. The addition of sitagliptin to ongoing metformin therapy significantly improves glycemic control in Chinese patients with type 2 diabetes[J]. J Diabetes, 2012,4(3):227-237.
[14] Yang W, Pan CY, Tou C, et al. Efficacy and safety of saxagliptin added to metformin in Asian people with type 2 diabetes mellitus:a randomized controlled trial[J]. Diabetes Res Clin Pract, 2011, 94(2):217-224.
[15] Dou J, Ma J, Liu J, et al. Efficacy and safety of saxagliptin in combination with metformin as initial therapy in Chinese patients with type 2 diabetes:Results from the START study, a multicentre, randomized, double-blind, activecontrolled, phase 3 trial[J]. Diabetes Obes Metab, 2018, 20(3):590-598.
[16] Gu W, Liang L, Wang S, et al. Efficacy and safety of saxagliptin monotherapy or added to metformin in Chinese patients with type 2diabetes mellitus:results from the 24-week, post-marketing SUNSHINE study[J]. J Diabetes, 2016, 8(6):809-815.
[17] Pan C, Xing X, Han P, et al. Efficacy and tolerability of vildagliptin as add-on therapy to metformin in Chinese patients with type 2 diabetes mellitus[J]. Diabetes Obes Metab, 2012, 14(8):737-744.
[18] Ji LN, Pan CY, Lu JM, et al. Efficacy and safety of combination therapy with vildagliptin and metformin versus metformin uptitration in Chinese patients with type 2 diabetes inadequately controlled with metformin monotherapy:a randomized, open-label, prospective study(VISION)[J].Diabetes Obes Metab, 2016, 18(8):775-782.
[19] Wang W, Yang J, Yang G, et al. Efficacy and safety of linagliptin in Asian patients with type 2 diabetes mellitus inadequately controlled by metformin:A multinational24-week, randomized clinical trial[J]. J Diabetes, 2016,8(2):229-237.
[20] Pan CY, Han P, Ji Q, et al. Efficacy and safety of alogliptin in patients with type 2 diabetes mellitus:A multicentre randomized double-blind placebo-controlled Phase 3 study in mainland China, Taiwan, and HongKong[J]. J Diabetes, 9(4):386-395.
[21] Xu W, Mu Y, Zhao J, et al. Efficacy and safety of metformin and sitagliptin based triple antihyperglycemic therapy(STRATEGY):a multicenter, randomized, controlled, non-inferiority clinical trial[J]. Sci China Life Sci, 2017, 60(3):225-238.
[22] Du J, Liang L, Fang H, et al. Efficacy and safety of saxagliptin compared with acarbose in Chinese patients with type 2 diabetes mellitus uncontrolled on metformin monotherapy:Results of a Phase IV open-label randomized controlled study(the SMART study)[J]. Diabetes Obes Metab, 2017,19(11):1513-1520.
[23] Del Prato S, Camisasca R, Wilson C, et al. Durability of the efficacy and safety of alogliptin compared with glipizide in type 2 diabetes mellitus:a2-year study. Diabetes Obes Metab, 2014, 16(12):1239-1246.
[24]陈光明,胡艳飞,楼雪勇.单用二甲双胍控制不佳的2型糖尿病患者联合沙格列汀或格列美脲的临床研究[J].中国临床药理学杂志,2015,31(19):1910-1912.
[25] Yang W Y, Xing X, Lv X, et al. Vildagliptin added to sulfonylurea improves glycemic control without hypoglycemia and weight gain in Chinese patients with type 2 diabetes mellitus[J]. J Diabetes, 2015, 7(2):174-181.
[26] Ba J, Han P, Yuan G, et al. Randomized trial assessing the safety and efficacy of sitagliptin in Chinese patients with type 2 diabetes mellitus inadequately controlled on sulfonylurea alone or combined with metformin[J]. J Diabetes, 2017, 9(7):667-676.
[27] Shankar RR, Bao Y, Han P, et al. Sitagliptin added to stable insulin therapy with or without metformin in Chinese patients with type 2diabetes[J]. J Diabetes Investig, 2017, 8(3):321-329.
[28] Ning G, Wang W, Li L, et al. Vildagliptin as add-on therapy to insulin improves glycemic control without increasing risk of hypoglycemia in Asian, predominantly Chinese, patients with type 2 diabetes mellitus[J].J Diabetes, 2016, 8(3):345-353.
[29] Chen Y, Liu X, Li Q, et al. Saxagliptin add-on therapy in Chinese patients with type 2 diabetes inadequately controlled by insulin with or without metformin:Results from the SUPER study, a randomized, double-blind,placebo-controlled trial. Diabetes Obes Metab, 2018,20(4):1044-1049.
[30] Monami M, Ahren B, Dicembrini I, et al. Dipeptidyl peptidase-4inhibitors and cardiovascular risk:a meta-analysis of randomized clinical trials[J]. Diabetes Obes Metab, 2013, 15(2):112-120.
[31] Kaneko M, Narukawa M. Meta-analysis of dipeptidyl peptidase-4inhibitors use and cardiovascular risk in patients with type 2 diabetes mellitus[J]. Diabetes Res Clin Pract, 2016, 116:171-182.
[32] Gokhale M, Buse JB, Jonsson Funk M, et al. No increased risk of cardiovascular events in older adults initiating dipeptidyl peptidase-4 inhibitors vs therapeutic alternatives[J]. Diabetes Obes Metab, 2017, 19(7):970-978.
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