达格列净在2型糖尿病患者中的应用与影响
Application and Influence of Dapagliflozin in Patients with Type 2 Diabetes Mellitus
DOI: 10.12677/MD.2023.133041, PDF,   
作者: 王永萍*：济宁医学院临床医学院，山东 济宁；刘亚平#：济宁市第一人民医院内分泌科，山东 济宁；山东大学药学院，山东 济南；辰欣药业股份有限公司，山东 济宁；卢秀莲：辰欣药业股份有限公司，山东 济宁
关键词: 达格列净；钠–葡萄糖共转运蛋白2抑制剂；2型糖尿病；Dapagliflozin； Sodium-Glucose Cotransporter 2 Inhibitor； Type 2 Diabetes Mellitus
摘要: 糖尿病发病率逐渐升高，其中2型糖尿病约占90%，2型糖尿病是一种发病机制复杂的慢性疾病，主要以胰岛素分泌不足或胰岛素抵抗为特征，其并发症严重影响人们的生活质量、威胁人们的生命健康。达格列净作为一种钠–葡萄糖共转运蛋白2抑制剂，不依赖于胰岛素发挥作用，除了控制血糖外，还可降低体重、血压、改善血脂，更重要的是近几年人们还发现其在心肾保护等方面也发挥重要作用。本文主要阐述达格列净在2型糖尿病患者中的主要应用及影响，旨在为临床用药提供参考。
Abstract: The morbidity of diabetes is gradually increasing, among which type 2 diabetes accounts for about 90%. Type 2 diabetes is a chronic disease with complex pathogenesis, mainly characterized by in-sulin deficiency or insulin resistance, and its complications seriously affect people’s quality of life and threaten people’s life and health. Dapagliflozin, as a sodium-glucose cotransporter 2 inhibitor, does not depend on insulin. In addition to control the blood glucose level, dapagliflozin can also re-duce body weight, blood pressure and improve blood lipids. More importantly, in recent years, peo-ple have found that it also plays an important role in the protection of heart and kidney. This article mainly describes the main application and influence of dapagliflozin in patients with type 2 diabe-tes mellitus, in order to provide reference for clinical medication.
文章引用：王永萍, 刘亚平, 卢秀莲. 达格列净在2型糖尿病患者中的应用与影响[J]. 医学诊断, 2023, 13(3): 262-270. https://doi.org/10.12677/MD.2023.133041

参考文献

[1] Saeedi, P., Petersohn, I., Salpea, P., et al. (2019) Global and Regional Diabetes Prevalence Estimates for 2019 and Projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th Edition. Diabetes Research and Clin-ical Practice, 157, Article ID: 107843. [Google Scholar] [CrossRef] [PubMed]
[2] Tan, S.Y., Wong, J., Yan, J.S., et al. (2019) Type 1 and 2 Diabetes Mellitus: A Review on Current Treatment Approach and Gene Therapy as Potential Inter-vention. Diabetes and Metabolic Syndrome: Clinical Research and Reviews, 13, 364-372. [Google Scholar] [CrossRef] [PubMed]
[3] Bommer, C., Heesemann, E., Sagalova, V., et al. (2017) The Global Eco-nomic Burden of Diabetes in Adults Aged 20-79 Years: A Cost-of-Illness Study. The Lancet Diabetes & Endocrinology, 5, 423-430. [Google Scholar] [CrossRef] 
[4] 中华医学会糖尿病学分会. 中国2型糖尿病防治指南(2020年版) [J]. 国际内分泌代谢杂志, 2021, 41(5): 482-548.
[5] Scheen, A.J. (2020) Sodium—Glucose Cotransporter Type 2 In-hibitors for the Treatment of Type 2 Diabetes Mellitus. Nature Reviews Endocrinology, 16, 556-577. [Google Scholar] [CrossRef] [PubMed]
[6] Wheeler, D.C., Stefánsson, B.V., Jongs, N., et al. (2021) Effects of Dapagliflozin on Major Adverse Kidney and Cardiovascular Events in Patients with Diabetic and Non-Diabetic Chronic Kidney Disease: A Prespecified Analysis from the DAPA-CKD Trial. The lancet Diabetes & Endocrinology, 9, 22-31. [Google Scholar] [CrossRef] 
[7] Mosenzon, O., Raz, I., Wiviott, S.D., et al. (2022) Dapagliflozin and Prevention of Kidney Disease among Patients with Type 2 Diabetes: Post Hoc Analyses from the DECLARE-TIMI 58 Trial. Diabetes Care, 45, 2350-2359. [Google Scholar] [CrossRef] [PubMed]
[8] Saisho, Y. (2020) SGLT2 Inhibitors: The Star in the Treatment of Type 2 Diabetes? Diseases, 8, Article 14. [Google Scholar] [CrossRef] [PubMed]
[9] Nicholson, M.K., Ghazal Asswad, R. and Wilding, J.P. (2021) Dapagli-flozin for the Treatment of Type 2 Diabetes Mellitus—An Update. Expert Opinion on Pharmacotherapy, 22, 2303-2310. [Google Scholar] [CrossRef] [PubMed]
[10] Kaku, K., Inoue, S., Matsuoka, O., et al. (2013) Efficacy and Safety of Dapagliflozin as a Monotherapy for Type 2 Diabetes Mellitus in Japanese Patients with Inadequate Glycaemic Control: A Phase II Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial. Diabetes, Obesity and Metabolism, 15, 432-440. [Google Scholar] [CrossRef] [PubMed]
[11] Yang, W.Y., Ma, J.H., Li, Y.M., et al. (2018) Dapagliflozin as Add-on Therapy in Asian Patients with Type 2 Diabetes Inadequately Controlled on Insulin with or without Oral Antihyperglycemic Drugs: A Randomized Controlled Trial. Journal of Diabetes, 10, 589-599. [Google Scholar] [CrossRef] [PubMed]
[12] 严玲玲, 林树云, 马丽丽. 达格列净联合二甲双胍治疗2型糖尿病的临床疗效和安全性[J]. 临床合理用药杂志, 2022, 15(16): 91-93.
[13] 马静. 达格列净治疗2型糖尿病患者的应用进展[J]. 现代诊断与治疗, 2021, 32(16): 2544-2545, 2589.
[14] Cai, X., Yang, W., Gao, X., et al. (2018) The Association between the Dosage of SGLT2 Inhibitor and Weight Re-duction in Type 2 Diabetes Patients: A Meta-Analysis. Obesity, 26, 70-80. [Google Scholar] [CrossRef] [PubMed]
[15] Chen, M.B., Wang, H., Cui, W.Y., Xu, H.L., et al. (2021) Effect of SGLT Inhibitors on Weight and Lipid Metabolism at 24 Weeks of Treatment in Patients with Diabetes Mellitus: A Systematic Review and Network Meta-Analysis. Medicine, 100, e24593. [Google Scholar] [CrossRef] 
[16] Sternlicht, H. and Bakris, G.L. (2019) Blood Pressure Lowering and Sodium-Glucose Co-Transporter 2 Inhibitors (SGLT2is): More Than Osmotic Diuresis. Current Hypertension Reports, 21, Article No. 12. [Google Scholar] [CrossRef] [PubMed]
[17] Jia, G. and Sowers, J.R. (2021) Hypertension in Diabetes: An Update of Basic Mechanisms and Clinical Disease. Hypertension, 78, 1197-1205. [Google Scholar] [CrossRef] 
[18] Morisco, C., Condorelli, G., Trimarco, V., et al. (2005) Akt Mediates the Cross-Talk Between β-Adrenergic and Insulin Receptors in Neonatal Cardiomyocytes. Circulation Research, 96, 180-188. [Google Scholar] [CrossRef] 
[19] Hao, Z., Sun, Y., Wen, Y., et al. (2020) Effects and Mecha-nisms of Dapagliflozin Treatment on Ambulatory Blood Pressure in Diabetic Patients with Hypertension. Medical Science Mon-itor, 26, e925987. [Google Scholar] [CrossRef] 
[20] Gallo, L.A., Ward, M.S., Fotheringham, A.K., et al. (2016) Once Daily Ad-ministration of the SGLT2 Inhibitor, Empagliflozin, Attenuates Markers of Renal Fibrosis without Improving Albuminuria in Diabetic db/db Mice. Scientific Reports, 6, Article No. 26428. [Google Scholar] [CrossRef] [PubMed]
[21] Kravtsova, O., Bohovyk, R., Levchenko, V., et al. (2022) SGLT2 Inhibition Effect on Salt-Induced Hypertension, RAAS, and Na+ Transport in Dahl SS Rats. American Journal of Physiology-Renal Physiology, 322, F692-F707. [Google Scholar] [CrossRef] [PubMed]
[22] 张楠, 阮丹杰, 刘新颖, 等. 达格列净对2型糖尿病合并高血压患者醛固酮/肾素浓度比值的影响[J]. 中华糖尿病杂志, 2022, 14(1): 63-67.
[23] Akash, M.S.H., Rehman, K. and Liaqat, A. (2018) Tumor Necrosis Factor-α: Role in Development of Insulin Resistance and Pathogenesis of Type 2 Diabetes Mellitus. Journal of Cellular Biochemistry, 119, 105-110. [Google Scholar] [CrossRef] [PubMed]
[24] Akbari, M. and Hassan-Zadeh, V. (2018) IL-6 Signalling Pathways and the De-velopment of Type 2 Diabetes. Inflammopharmacology, 26, 685-698. [Google Scholar] [CrossRef] [PubMed]
[25] Nedosugova, L.V., Markina, Y.V., Bochkareva, L.A., et al. (2022) In-flammatory Mechanisms of Diabetes and Its Vascular Complications. Biomedicines, 10, Article 1168. [Google Scholar] [CrossRef] [PubMed]
[26] Wang, C., Qin, Y., Zhang, X., et al. (2022) Effect of Dapagliflozin on Indicators of Myocardial Fibrosis and Levels of Inflammatory Factors in Heart Failure Patients. Disease Markers, 2022, Article ID: 5834218. [Google Scholar] [CrossRef] [PubMed]
[27] Contreras-Bolívar, V., García-Fontana, B., García-Fontana, C. and Muñoz-Torres, M. (2021) Mechanisms Involved in the Relationship between Vitamin D and Insulin Resistance: Impact on Clinical Practice. Nutrients, 13, Article 3491. [Google Scholar] [CrossRef] [PubMed]
[28] 骆莹莹, 黄若妃, 李可. 达格列净对2型糖尿病患者25(OH)D_3及炎症因子表达的影响[J]. 重庆医学, 2022, 51(12): 2024-2027.
[29] 赵梦萍, 孔祥栋, 陈肖蓉, 等. 达格列净治疗早期糖尿病肾病的疗效及对血清TNF-α、IL-6水平的影响[J]. 中国现代医生, 2022, 60(14): 33-36.
[30] Leoncini, G., Russo, E., Bus-salino, E., Barnini, C., et al. (2021) SGLT2is and Renal Protection: From Biological Mechanisms to Real-World Clinical Bene-fits. International Journal of Molecular Sciences, 22, Article 4441. [Google Scholar] [CrossRef] [PubMed]
[31] Ambarsari, C.G., Pardede, S.O., Fazlur Rahman, F.H., et al. (2021) Role of Dipstick Albuminuria in Progression of Paediatric Chronic Kidney Disease. Journal of the Pakistan Medical Association, 71, S103-S106.
[32] Wu, L., Liu, C., Chang, D.Y., et al. (2021) Annexin A1 Alleviates Kidney Injury by Promoting the Resolu-tion of Inflammation in Diabetic Nephropathy. Kidney International, 100, 107-121. [Google Scholar] [CrossRef] [PubMed]
[33] Kelly, M.S., Lewis, J., Huntsberry, A.M., Dea, L. and Portillo, I. (2019) Efficacy and Renal Outcomes of SGLT2 Inhibitors in Patients with Type 2 Diabetes and Chronic Kidney Disease. Postgraduate Medicine, 131, 31-42. [Google Scholar] [CrossRef] [PubMed]
[34] Bailey, C.J., Day, C. and Bellary, S. (2022) Renal Protection with SGLT2 Inhibitors: Effects in Acute and Chronic Kidney Disease. Current Diabetes Reports, 22, 39-52. [Google Scholar] [CrossRef] [PubMed]
[35] Kanbay, M., Tapoi, L., Ureche, C., et al. (2022) Effect of Sodi-um-Glucose Cotransporter 2 Inhibitors on Hemoglobin and Hematocrit Levels in Type 2 Diabetes: A Systematic Review and Meta-Analysis. International Urology and Nephrology, 54, 827-841. [Google Scholar] [CrossRef] [PubMed]
[36] Heerspink, H.J., Stefánsson, B.V., Correa-Rotter, R., et al. (2020) Dapagliflozin in Patients with Chronic Kidney Disease. The New England Journal of Medicine, 383, 1436-1446. [Google Scholar] [CrossRef] 
[37] Heerspink, H.J.L., Jongs, N., Chertow, G.M., et al. (2021) Effect of Dapagliflozin on the Rate of Decline in Kidney Function in Patients with Chronic Kidney Disease with and without Type 2 Dia-betes: A Prespecified Analysis from the DAPA-CKD Trial. The Lancet Diabetes & Endocrinology, 9, 743-754. [Google Scholar] [CrossRef] 
[38] American Diabetes Association Professional Practice Committee (2022) 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes—2022. Diabetes Care, 45, S125-S143. [Google Scholar] [CrossRef] 
[39] Wiviott, S.D., Raz, I., Bonaca, M.P., et al. (2019) Dapagliflozin and Cardiovascu-lar Outcomes in Type 2 Diabetes. The New England Journal of Medicine, 380, 347-357. [Google Scholar] [CrossRef] 
[40] Zelniker, T.A., Bonaca, M.P., Furtado, R.H., et al. (2020) Effect of Dapagliflozin on Atrial Fibrillation in Patients with Type 2 Diabetes Mellitus: Insights from the DECLARE-TIMI 58 Trial. Cir-culation, 141, 1227-1234. [Google Scholar] [CrossRef] 
[41] Ong, H.T., Teo, Y.H., Teo, Y.N., et al. (2022) Effects of Sodium/Glucose Cotransporter Inhibitors on Atrial Fibrillation and Stroke: A Meta-Analysis. Journal of Stroke and Cerebro-vascular Diseases, 31, Article ID: 106159. [Google Scholar] [CrossRef] [PubMed]
[42] McMurray, J.J.V., Solomon, S.D., Inzucchi, S.E., et al. (2019) Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. The New England Journal of Medicine, 381, 1995-2008. [Google Scholar] [CrossRef] 
[43] Vaduganathan, M., Docherty, K.F., Claggett, B.L., et al. (2022) SGLT-2 Inhibitors in Patients with Heart Failure: A Comprehensive Meta-Analysis of Five Randomised Controlled Trials. The Lancet, 400, 757-767. [Google Scholar] [CrossRef] 
[44] Solomon, S.D., McMurray, J.J.V., Claggett, B., et al. (2022) Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. The New England Journal of Medicine, 387, 1089-1098. [Google Scholar] [CrossRef] 
[45] Jhund, P.S., Kondo, T., Butt, J.H., et al. (2022) Dapagliflozin across the Range of Ejection Fraction in Patients with Heart Failure: A Patient-Level, Pooled Meta-Analysis of DAPA-HF and DELIVER. Nature Medicine, 28, 1956-1964. [Google Scholar] [CrossRef] [PubMed]
[46] Lopaschuk, G.D. and Verma, S. (2020) Mechanisms of Cardiovascular Benefits of Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors: A State-of-the-Art Review. JACC: Basic to Translational Science, 5, 632-644. [Google Scholar] [CrossRef] [PubMed]
[47] Grandoch, M., Kohlmorgen, C., Melchior-Becker, A., et al. (2016) Loss of Biglycan Enhances Thrombin Generation in Apolipoprotein E-Deficient Mice: Implications for Inflammation and Atheroscle-rosis. Arteriosclerosis, Thrombosis, and Vascular Biology, 36, e41-e50. [Google Scholar] [CrossRef] 
[48] Kohlmorgen, C., Gerfer, S., Feldmann, K., et al. (2021) Dapagli-flozin Reduces Thrombin Generation and Platelet Activation: Implications for Cardiovascular Risk Reduction in Type 2 Diabetes Mellitus. Diabetologia, 64, 1834-1849. [Google Scholar] [CrossRef] [PubMed]
[49] Lee, T.M., Chang, N.C. and Lin, S.Z. (2017) Dapagliflozin, a Selective SGLT2 Inhibitor, Attenuated Cardiac Fibrosis by Regulating the Macrophage Polarization via STAT3 Signaling in Infarcted Rat Hearts. Free Radical Biology and Medicine, 104, 298-310. [Google Scholar] [CrossRef] [PubMed]
[50] Baartscheer, A., Schumacher, C.A., Wüst, R.C., et al. (2017) Empagliflozin Decreases Myocardial Cytoplasmic Na+ through Inhibition of the Cardiac Na+/H+ Exchanger in Rats and Rabbits. Diabetologia, 60, 568-573. [Google Scholar] [CrossRef] [PubMed]
[51] Chung, Y.J., Park, K.C., Tokar, S., et al. (2021) Off-Target Effects of Sodium-Glucose Co-Transporter 2 Blockers: Empagliflozin Does Not Inhibit Na+/H+ Exchanger-1 or Lower [Na+]i in the Heart. Cardiovascular Research, 117, 2794-2806. [Google Scholar] [CrossRef] [PubMed]
[52] Xu, B., Li, S.Q., Kang, B. and Zhou, J.C. (2022) The Current Role of Sodium-Glucose Cotransporter 2 Inhibitors in Type 2 Diabetes Mellitus Management. Cardiovascular Diabetology, 21, Article No. 83. [Google Scholar] [CrossRef] [PubMed]
[53] Davidson, J.A., Sukor, N., Hew, F.L., Mohamed, M. and Hussein, Z. (2023) Safety of Sodium-Glucose Cotransporter 2 Inhibitors in Asian Type 2 Diabetes Populations. Journal of Diabetes Investigation, 14, 167-182. [Google Scholar] [CrossRef] [PubMed]
[54] Chowdhury, T., Gousy, N., Bellamkonda, A., et al. (2022) Fournier’s Gangrene: A Coexistence or Consanguinity of SGLT-2 Inhibitor Therapy. Cureus, 14, e27773. [Google Scholar] [CrossRef] [PubMed]
[55] Qiu, M., Ding, L.L., Zhang, M. and Zhou, H.R. (2021) Safety of Four SGLT2 Inhibitors in Three Chronic Diseases: A Meta-Analysis of Large Randomized Trials of SGLT2 Inhibitors. Diabetes and Vascu-lar Disease Research, 18, No. 2. [Google Scholar] [CrossRef] [PubMed]
[56] Hapca, S., Siddiqui, M.K., Kwan, R.S.Y., et al. (2021) The Relation-ship between AKI and CKD in Patients with Type 2 Diabetes: An Observational Cohort Study. Journal of the American Society of Nephrology, 32, 138-150. [Google Scholar] [CrossRef] 
[57] Zhuo, M., Paik, J.M., Wexler, D.J., et al. (2022) SGLT2 Inhibitors and the Risk of Acute Kidney Injury in Older Adults with Type 2 Diabetes. American Journal of Kidney Diseases, 79, 858-867.E1. [Google Scholar] [CrossRef] [PubMed]