Research progress of Empagliflozin in the treatment of type 2 diabetes mellitus
HUO Qidong LI Deguan#br#
Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Tianjin 300192, China
Abstract：Type 2 diabetes mellitus is one of the most common chronic metabolic diseases worldwide. Traditional drug therapy of type 2 diabetes mellitus relies on the regulation of insulin and is associated with multiple side effects. Sodium-glucose co-transporter-2 is a new therapeutic target for type 2 diabetes mellitus identified in recent years. Empagliflozin, one of the SGLT-2 inhibitors, approved and shown excellent glucose-lowering effects and safety in the diabetes treatment, has been widely used in clinic therapy. Empagliflozin also has the functions of reducing oxidative stress, inhibiting inflammatory response, and regulating apoptosis. This article summarizes the therapeutic advances and mechanisms of Empagliflozin in type 2 diabetes mellitus, with a view to providing more ideas for clinical treatment of patients with type 2 diabetes mellitus and expanding the indications of Empagliflozin.
霍启东 李德冠. 恩格列净在2型糖尿病治疗中的研究进展[J]. 中国医药导报, 2023, 20(16): 37-40,49.
HUO Qidong LI Deguan. Research progress of Empagliflozin in the treatment of type 2 diabetes mellitus. 中国医药导报, 2023, 20(16): 37-40,49.
[1] Cho NH，Shaw JE，Karuranga S，et al. IDF Diabetes Atlas：Global estimates of diabetes prevalence for 2017 and projections for 2045 [J]. Diabetes Res Clin Pract，2018，138：271- 281.
[2] Bhosle D，Indurkar S，Quadri U，et al. A Comparative Study of efficacy and safety of different Sodium Glucose Co-transporter 2（SGLT-2）Inhibitors in the Management of Patients with Type Ⅱ Diabetes Mellitus [J]. J Assoc Physicians India，2022，70（6）：11-12.
[3] Chawla G，Chaudhary KK. A complete review of empagliflozin：Most specific and potent SGLT2 inhibitor used for the treatment of type 2 diabetes mellitus [J]. Diabetes Metab Syndr，2019，13（3）：2001-2008.
[4] Hussain M，Elahi A，Iqbal J，et al. Comparison of Efficacy and Safety Profile of Sodium-Glucose Cotransporter-2 Inhibitors as Add-On Therapy in Patients with Type 2 Diabetes [J]. Cureus，2021，13（4）：e14268.
[5] Bhosle D，Chavan S，Kardile S. Efficacy and Safety of Empag- liflozin as Add on in Patients with Type Ⅱ Diabetes Mellitus（DM）Inadequately Controlled on Triple Drug Combination [J]. J Assoc Physicians India，2022，69（12）：11-12.
[6] 陈本川.治疗2型糖尿病新药——恩格列净（empaglif- lozin）[J].医药导报，2015，34（2）：284-289.
[7] Anderson JE，Wright Jr EE，Shaefer Jr CF. Empagliflozin：Role in Treatment Options for Patients with Type 2 Diabetes Mellitus [J]. Diabetes Ther，2017，8（1）：33-53.
[8] Zou R，Shi W，Qiu J，et al. Empagliflozin attenuates cardiac microvascular ischemia/reperfusion injury through improving mitochondrial homeostasis [J]. Cardiovasc Diabetol，2022，21（1）：106.
[9] Lopaschuk GD，Verma S. Mechanisms of Cardiovascular Ben- efits of Sodium Glucose Co-Transporter 2（SGLT2）Inhibitors： A State-of-the-Art Review [J]. JACC Basic Transl Sci，2020， 5（6）：632-644.
[10] Kusaka H，Koibuchi N，Hasegawa Y，et al. Empagliflozin lessened cardiac injury and reduced visceral adipocyte hypertrophy in prediabetic rats with metabolic syndrome [J]. Cardiovasc Diabetol，2016，15（1）：157.
[11] Zhou H，Wang SY，Zhu PJ，et al. Empagliflozin rescues diabetic myocardial microvascular injury via AMPK-mediated inhibition of mitochondrial fission [J]. Redox Biol，2018， 15：335-346.
[12] Hussein AM，Eid EA，Taha M，et al. Comparative Study of the Effects of GLP1 Analog and SGLT2 Inhibitor against Diabetic Cardiomyopathy in Type 2 Diabetic Rats：Possible Underlying Mechanisms [J]. Biomedicines，2020，8（3）：43.
[13] Lu YH，Chang YP，Li T，et al. Empagliflozin Attenuates Hyperuricemia by Upregulation of ABCG2 via AMPK/AKT/ CREB Signaling Pathway in Type 2 Diabetic Mice [J]. Int JBiol Sci，2020，16（3）：529-542.
[14] Lin TA，Wu VC，Wang CY. Autophagy in Chronic Kidney Diseases [J]. Cells，2019，8（1）：61.
[15] Lee YH，Kim SH，Kang JM，et al. Empagliflozin attenuates diabetic tubulopathy by improving mitochondrial fragmentation and autophagy [J]. Am J Physiol Renal Physiol，2019， 317（4）：F767-F780.
[16] Korbut AI，Taskaeva IS，Bgatova NP，et al. SGLT2 Inhibitor Empagliflozin and DPP4 Inhibitor Linagliptin Reactivate Glomerular Autophagy in db/db Mice，a Model of Type 2 Diabetes [J]. Int J Mol Sci，2020，21（8）：2987.
[17] Provenzano M，Pelle MC，Zaffina I，et al. Sodium-Glucose Co-transporter-2 Inhibitors and Nephroprotection in Diabetic Patients：More Than a Challenge [J]. Front Med （Lausanne），2021，8：654557.
[18] Tanase DM，Gosav EM，Costea CF，et al. The Intricate Relationship between Type 2 Diabetes Mellitus（T2DM），Insulin Resistance（IR），and Nonalcoholic Fatty Liver Disease（NAFLD） [J]. J Diabetes Res，2020，2020：3920196.
[19] Kahl S，Gancheva S，Strassburger K，et al. Empagliflozin Effe- ctively Lowers Liver Fat Content in Well-Controlled Type 2 Diabetes：A Randomized，Double-Blind，Phase 4，Placebo-Controlled Trial [J]. Diabetes Care，2020，43（2）：298- 305.
[20] Lai LL，Vethakkan SR，Nik Mustapha NR，et al. Empagli- flozin for the Treatment of Nonalcoholic Steatohepatitis in Patients with Type 2 Diabetes Mellitus [J]. Dig Dis Sci，2020， 65（2）：623-631.
[21] Lv QY，Le L，Xiang JM，et al. Liver Transcriptomic Reveals Novel Pathways of Empagliflozin Associated With Type 2 Diabetic Rats [J]. Front Endocrinol，2020，11：111.
[22] Li T，Fang T，Xu LX，et al. Empagliflozin Alleviates Hepatic Steatosis by Activating the AMPK-TET2-Autophagy Pathway in vivo and in vitro [J]. Front Pharmacol，2020，11： 622153.
[23] Wang Y，Ding Y，Sun P，et al. Empagliflozin-Enhanced Ant- ioxidant Defense Attenuates Lipotoxicity and Protects Hepatocytes by Promoting FoxO3a- and Nrf2-Mediated Nuclear Translocation via the CAMKK2/AMPK Pathway [J]. Antioxidants（Basel），2022，11（5）：799.
[24] Ninomiya T. Epidemiological Evidence of the Relationship Between Diabetes and Dementia [J]. Adv Exp Med Biol，2019， 1128：13-25.
[25] Wang Y，Westermark GT. The Amyloid Forming Peptides Islet Amyloid Polypeptide and Amyloid β Interact at the Molecular Level [J]. Int J Mol Sci，2021，22（20）：11153.
[26] Lin KJ，Wang TJ，Chen SD，et al. Two Birds One Stone：The Neuroprotective Effect of Antidiabetic Agents on Parkinson Disease-Focus on Sodium-Glucose Cotransporter 2（SGLT2）Inhibitors [J]. Antioxidants（Basel），2021，10（12）：1935.
[27] Heimke M，Lenz F，Rickert U，et al. Anti-Inflammatory Pro- perties of the SGLT2 Inhibitor Empagliflozin in Activated Primary Microglia [J]. Cells，2022，11（19）：3107.
[28] Hierro-bujalance C，Infante-garcia C，Del marco A，et al. Empagliflozin reduces vascular damage and cognitive impairment in a mixed murine model of Alzheimer’s disease and type 2 diabetes [J]. Alzheimer Res Ther，2020， 12（1）： 40.
[29] Motawi TK，Al-Kady RH，Abdelraouf SM，et al. Empagl-iflozin alleviates endoplasmic reticulum stress and augments autophagy in rotenone-induced Parkinson’s disease in rats：Targeting the GRP78/PERK/eIF2alpha/CHOP pathway and miR-211-5p [J]. Chem Biol Interact， 2022， 362：110002.
[30] Ha MJ，Choi SY，Kim M，et al. Diabetic Nephropathy in Type 2 Diabetic Retinopathy Requiring Panretinal Photocoagulation [J]. Korean J Ophthalmol，2019，33（1）：46-53.
[31] Matthews J，Herat L，Rooney J，et al. Determining the role of SGLT2 inhibition with Empagliflozin in the development of diabetic retinopathy [J]. Biosci Rep，2022，42（3）：BSR20 212209.
[32] Gong QY，Zhang RL，Wei F，et al. SGLT2 inhibitor-empag- liflozin treatment ameliorates diabetic retinopathy manifestations and exerts protective effects associated with augmenting branched chain amino acids catabolism and transportation in db/db mice [J]. Biomed Pharmacother，2022， 152：113222.
[33] Chen Z，Li G. Sodium-Glucose Co-Transporter 2 Inhibitors Compared with Sulfonylureas in Patients with Type 2 Diabetes Inadequately Controlled on Metformin：A Meta-Analysis of Randomized Controlled Trials [J]. Clin Drug Investig，2019，39（6）：521-531.
[34] Kurtz R，Libby A，Jones BA，et al. Empagliflozin Treatment Attenuates Hepatic Steatosis by Promoting White Adipose Expansion in Obese TallyHo Mice [J]. Int J Mol Sci，2022， 23（10）：56175.
[35] Liakos CI，Papadopoulos DP，Sanidas EA，et al. Blood Pressure- Lowering Effect of Newer Antihyperglycemic Agents（SGLT-2 Inhibitors，GLP-1 Receptor Agonists，and DPP-4 Inhibitors）[J]. Am J Cardiovasc Drugs，2021，21（2）：123- 137.
[36] Lahnwong S，Chattipakorn SC，Chattipakorn N. Potential mechanisms responsible for cardioprotective effects of sodium-glucose co-transporter 2 inhibitors [J]. Cardiovasc Diabetol，2018，17（1）：101.
[37] 张爱敏，高宇.2型糖尿病合并心血管并发症患者肠道菌群特征的研究进展[J].中华糖尿病杂志，2021，13（5）：526-529.
[38] Deng X，Zhang C，Wang P，et al. Cardiovascular benefits of empagliflozin are associated with gut microbiota and plasma metabolites in type 2 diabetes [J]. J Clin Endocrinol Metab，2022，107（7）：1888-1896.
[39] Pinaud L，Sansonetti PJ，Phalipon A. Host Cell Targeting by Enteropathogenic Bacteria T3SS Effectors [J]. Trends Mic- robiol，2018，26（4）：266-283.
[40] Mehta S，Nain P，Agrawal BK，et al. Effectiveness of Empagliflozin With Vitamin D Supplementation in Peripheral Neuropathy in Type 2 Diabetic Patients [J]. Cureus，2021， 13（12）：e20208.
[41] Siamashvili M，Davis SN. Sodium-glucose cotransporter 2 inhibitors for the management of type 2 diabetes [J]. Expert Opin Pharmacother，2021，22（16）：2181-2198.
[42] Shin H，Schneeweiss S，Glynn RJ，et al. Cardiovascular Out- comes in Patients Initiating First-Line Treatment of Type 2 Diabetes With Sodium-Glucose Cotransporter-2 Inhibitors Versus Metformin：A Cohort Study [J]. Ann Intern Med，2022，175（7）：927-937.
[43] Al-wakeel DE，El-kashef DH，Nader MA. Renoprotective effect of empagliflozin in cafeteria diet-induced insulin resistance in rats：Modulation of HMGB-1/TLR-4/NF-κB axis [J]. Life Sci，2022，301：120633.
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