The Role of SGLT2 Inhibitor on the Treatment of Diabetic Retinopathy

Wenjun Sha, Song Wen, Lin Chen, Bilin Xu, Tao Lei, Ligang Zhou, Wenjun Sha, Song Wen, Lin Chen, Bilin Xu, Tao Lei, Ligang Zhou

Abstract

Diabetic retinopathy (DR) is one of the most serious complications of diabetic microangiopathy. DR has an early onset and is not easy to detect. When visual impairment occurs, the optimal period for therapy is often missed. Therefore, the prevention and treatment of DR should start from the early stage of diabetes. Sodium-dependent glucose transporter 2 inhibitor (SGLT2i) is a new antidiabetic drug which is mainly used in clinical practice to control blood glucose of patients with type 2 diabetes prone to develop chronic heart failure. Recent studies have found that SGLT2 is also expressed in the human retina. Now, the prevention and treatment of diabetic retinopathy with SGLT2i while reducing blood sugar has become a new research field. Hence, this article reviewed the recent therapeutic and research progress of SGLT2 in the treatment of diabetic retinopathy.

Conflict of interest statement

The authors declare no conflict of interest.

Copyright © 2020 Wenjun Sha et al.

Figures

Figure 1
Figure 1
The proposed mechanism of SGLT2 inhibitor (SGLT2i) against diabetic retinopathy, in which SGLT2i improves hyperlipidemia, hyperglycemia, and hypertension.

References

    1. American Diabetes Association. 2. Classification and diagnosis of diabetes: standards of medical care in diabetes-2019. Diabetes Care. 2019;42(Supplement 1):S13–s28. doi: 10.2337/dc19-S002.
    1. Gong M., Wen S., Nguyen T., Wang C., Jin J., Zhou L. Converging relationships of obesity and hyperuricemia with special reference to metabolic disorders and plausible therapeutic implications. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 2020;13:943–962. doi: 10.2147/DMSO.S232377.
    1. Wen S., Wang C., Gong M., Zhou L. An overview of energy and metabolic regulation. Science China Life Sciences. 2019;62(6):771–790. doi: 10.1007/s11427-018-9371-4.
    1. Wong T. Y., Sabanayagam C. The war on diabetic retinopathy. Asia-Pacific Journal of Ophthalmology. 2019;8(6):448–456. doi: 10.1097/APO.0000000000000267.
    1. Giuliari G. P. Diabetic retinopathy: current and new treatment options. Current Diabetes Reviews. 2012;8(1):32–41. doi: 10.2174/157339912798829188.
    1. Ting D. S. W., Cheung G. C. M., Wong T. Y. Diabetic retinopathy: global prevalence, major risk factors, screening practices and public health challenges: a review. Clinical & Experimental Ophthalmology. 2016;44(4):260–277. doi: 10.1111/ceo.12696.
    1. Homme R. P., Singh M., Majumder A., et al. Remodeling of retinal architecture in diabetic retinopathy: disruption of ocular physiology and visual functions by inflammatory gene products and pyroptosis. Frontiers in Physiology. 2018;9:p. 1268. doi: 10.3389/fphys.2018.01268.
    1. Scanlon P. H., Aldington S. J., Stratton I. M. Epidemiological issues in diabetic retinopathy. Middle East African Journal of Ophthalmology. 2013;20(4):293–300. doi: 10.4103/0974-9233.120007.
    1. Hainsworth D. P., Bebu I., Aiello L. P., et al. Risk factors for retinopathy in type 1 diabetes: the DCCT/EDIC study. Diabetes Care. 2019;42(5):875–882. doi: 10.2337/dc18-2308.
    1. Kaku K., Inoue S., Matsuoka O., et al. 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 & Metabolism. 2013;15(5):432–440. doi: 10.1111/dom.12047.
    1. Semeraro F., Morescalchi F., Cancarini A., Russo A., Rezzola S., Costagliola C. Diabetic retinopathy, a vascular and inflammatory disease: therapeutic implications. Diabetes & Metabolism. 2019;45(6):517–527. doi: 10.1016/j.diabet.2019.04.002.
    1. Mesquida M., Drawnel F., Fauser S. The role of inflammation in diabetic eye disease. Seminars in Immunopathology. 2019;41(4):427–445. doi: 10.1007/s00281-019-00750-7.
    1. Spencer B. G., Estevez J. J., Liu E., Craig J. E., Finnie J. W. Pericytes, inflammation, and diabetic retinopathy. Inflammopharmacology. 2020;28(3):697–709. doi: 10.1007/s10787-019-00647-9.
    1. Ighodaro O. M. Molecular pathways associated with oxidative stress in diabetes mellitus. Biomedicine & Pharmacotherapy. 2018;108:656–662. doi: 10.1016/j.biopha.2018.09.058.
    1. Benlarbi-Ben Khedher M., Hajri K., Dellaa A., et al. Astaxanthin inhibits aldose reductase activity in Psammomys obesus, a model of type 2 diabetes and diabetic retinopathy. Food Science & Nutrition. 2019;7(12):3979–3985. doi: 10.1002/fsn3.1259.
    1. Mishra M., Duraisamy A. J., Bhattacharjee S., Kowluru R. A. Adaptor protein p66Shc: a link between cytosolic and mitochondrial dysfunction in the development of diabetic retinopathy. Antioxidants & Redox Signaling. 2019;30(13):1621–1634. doi: 10.1089/ars.2018.7542.
    1. Deissler H. L., Lang G. E. The protein kinase C inhibitor: ruboxistaurin. Developments in Ophthalmology. 2016;55:295–301. doi: 10.1159/000431204.
    1. Luo S., Shi C., Wang F., Wu Z. Association between the angiotensin-converting enzyme (ACE) genetic polymorphism and diabetic retinopathy-a meta-analysis comprising 10,168 subjects. International Journal of Environmental Research and Public Health. 2016;13(11, article 1142) doi: 10.3390/ijerph13111142.
    1. Ehrenkranz J. R. L., Lewis N. G., Ronald Kahn C., Roth J. Phlorizin: a review. Diabetes/Metabolism Research and Reviews. 2005;21(1):31–38. doi: 10.1002/dmrr.532.
    1. Uldry M., Thorens B. The SLC2 family of facilitated hexose and polyol transporters. Pflügers Archiv. 2004;447(5):480–489. doi: 10.1007/s00424-003-1085-0.
    1. Yakovleva T., Sokolov V., Chu L., et al. Comparison of the urinary glucose excretion contributions of SGLT2 and SGLT1: a quantitative systems pharmacology analysis in healthy individuals and patients with type 2 diabetes treated with SGLT2 inhibitors. Diabetes, Obesity & Metabolism. 2019;21(12):2684–2693. doi: 10.1111/dom.13858.
    1. May M., Framke T., Junker B., Framme C., Pielen A., Schindler C. How and why SGLT2 inhibitors should be explored as potential treatment option in diabetic retinopathy: clinical concept and methodology. Therapeutic Advances in Endocrinology and Metabolism. 2019;10, article 2042018819891886 doi: 10.1177/2042018819891886.
    1. Dziuba J., Alperin P., Racketa J., et al. Modeling effects of SGLT-2 inhibitor dapagliflozin treatment versus standard diabetes therapy on cardiovascular and microvascular outcomes. Diabetes, Obesity & Metabolism. 2014;16(7):628–635. doi: 10.1111/dom.12261.
    1. Stratton I. M., Adler A. I., Neil H. A., et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321(7258):405–412. doi: 10.1136/bmj.321.7258.405.
    1. Wang N. K., Lai C. C., Wang J. P., et al. Risk factors associated with the development of retinopathy 10 yr after the diagnosis of juvenile-onset type 1 diabetes in Taiwan: a cohort study from the CGJDES. Pediatric Diabetes. 2016;17(6):407–416. doi: 10.1111/pedi.12312.
    1. American Diabetes Association. 1. Improving care and promoting health in populations: standards of medical care in diabetes-2020. Diabetes Care. 2020;43(Supplement 1):S7–s13. doi: 10.2337/dc20-S001.
    1. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998;317(7160):703–713. doi: 10.1136/bmj.317.7160.703.
    1. Wang S., Xu L., Jonas J. B., et al. Major eye diseases and risk factors associated with systemic hypertension in an adult Chinese population. Ophthalmology. 2009;116(12):2373–2380. doi: 10.1016/j.ophtha.2009.05.041.
    1. Salvetti M., Agabiti Rosei C., Paini A., et al. Relationship of wall-to-lumen ratio of retinal arterioles with clinic and 24-hour blood pressure. Hypertension. 2014;63(5):1110–1115. doi: 10.1161/HYPERTENSIONAHA.113.03004.
    1. Merovci A., Solis-Herrera C., Daniele G., et al. Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production. The Journal of Clinical Investigation. 2014;124(2):509–514. doi: 10.1172/JCI70704.
    1. Peene B., Benhalima K. Sodium glucose transporter protein 2 inhibitors: focusing on the kidney to treat type 2 diabetes. Therapeutic Advances in Endocrinology and Metabolism. 2014;5(5):124–136. doi: 10.1177/2042018814553965.
    1. Shin S. J., Chung S., Kim S. J., et al. Effect of sodium-glucose co-transporter 2 inhibitor, dapagliflozin, on renal renin-angiotensin system in an animal model of type 2 diabetes. PLoS One. 2016;11(11, article e0165703) doi: 10.1371/journal.pone.0165703.
    1. Wang B., Wang F., Zhang Y., et al. Effects of RAS inhibitors on diabetic retinopathy: a systematic review and meta-analysis. The Lancet Diabetes and Endocrinology. 2015;3(4):263–274. doi: 10.1016/S2213-8587(14)70256-6.
    1. Dorsey-Treviño E. G., Contreras-Garza B. M., González-González J. G., et al. Systematic review and meta-analysis of the effect of SGLT-2 inhibitors on microvascular outcomes in patients with type 2 diabetes: a review protocol. BMJ Open. 2018;8(6, article e020692) doi: 10.1136/bmjopen-2017-020692.
    1. Zhang H. Y., Wang J. Y., Ying G. S., Shen L. P., Zhang Z. Serum lipids and other risk factors for diabetic retinopathy in Chinese type 2 diabetic patients. Journal of Zhejiang University Science B. 2013;14(5):392–399. doi: 10.1631/jzus.B1200237.
    1. Li J., Wang J. J., Chen D., et al. Systemic administration of HMG-CoA reductase inhibitor protects the blood-retinal barrier and ameliorates retinal inflammation in type 2 diabetes. Experimental Eye Research. 2009;89(1):71–78. doi: 10.1016/j.exer.2009.02.013.
    1. Filippas-Ntekouan S., Tsimihodimos V., Filippatos T., Dimitriou T., Elisaf M. SGLT-2 inhibitors: pharmacokinetics characteristics and effects on lipids. Expert Opinion on Drug Metabolism & Toxicology. 2018;14(11):1113–1121. doi: 10.1080/17425255.2018.1541348.
    1. Ferrannini E. Sodium-glucose co-transporters and their inhibition: clinical physiology. Cell Metabolism. 2017;26(1):27–38. doi: 10.1016/j.cmet.2017.04.011.
    1. Jo D. H., Yun J. H., Cho C. S., Kim J. H., Kim J. H., Cho C. H. Interaction between microglia and retinal pigment epithelial cells determines the integrity of outer blood-retinal barrier in diabetic retinopathy. Glia. 2019;67(2):321–331. doi: 10.1002/glia.23542.
    1. Wakisaka M., Yoshinari M., Nakamura S., et al. Suppression of sodium-dependent glucose uptake by captopril improves high-glucose-induced morphological and functional changes of cultured bovine retinal pericytes. Microvascular Research. 1999;58(3):215–223. doi: 10.1006/mvre.1999.2178.
    1. Roy S., Bae E., Amin S., Kim D. Extracellular matrix, gap junctions, and retinal vascular homeostasis in diabetic retinopathy. Experimental Eye Research. 2015;133:58–68. doi: 10.1016/j.exer.2014.08.011.
    1. Yoshizumi H., Ejima T., Nagao T., Wakisaka M. Recovery from diabetic macular edema in a diabetic patient after minimal dose of a sodium glucose co-transporter 2 inhibitor. Am J Case Rep. 2018;19:462–466. doi: 10.12659/AJCR.909708.
    1. Chen Y. Y., Wu T. T., Ho C. Y., et al. Dapagliflozin prevents NOX- and SGLT2-dependent oxidative stress in lens cells exposed to fructose-induced diabetes mellitus. International Journal of Molecular Sciences. 2019;20(18, article 4357) doi: 10.3390/ijms20184357.
    1. Takakura S., Toyoshi T., Hayashizaki Y., Takasu T. Effect of ipragliflozin, an SGLT2 inhibitor, on progression of diabetic microvascular complications in spontaneously diabetic Torii fatty rats. Life Sciences. 2016;147:125–131. doi: 10.1016/j.lfs.2016.01.042.
    1. Ott C., Jumar A., Striepe K., et al. A randomised study of the impact of the SGLT2 inhibitor dapagliflozin on microvascular and macrovascular circulation. Cardiovascular Diabetology. 2017;16(1):p. 26. doi: 10.1186/s12933-017-0510-1.
    1. Jumar A., Ott C., Kistner I., et al. Early signs of end-organ damage in retinal arterioles in patients with type 2 diabetes compared to hypertensive patients. Microcirculation. 2016;23(6):447–455. doi: 10.1111/micc.12291.
    1. Grunwald J. E., DuPont J., Riva C. E. Retinal haemodynamics in patients with early diabetes mellitus. The British Journal of Ophthalmology. 1996;80(4):327–331. doi: 10.1136/bjo.80.4.327.
    1. Patel V., Rassam S., Newsom R., Wiek J., Kohner E. Retinal blood flow in diabetic retinopathy. BMJ. 1992;305(6855):678–683. doi: 10.1136/bmj.305.6855.678.
    1. Simó-Servat O., Simó R., Hernández C. Circulating biomarkers of diabetic retinopathy: an overview based on physiopathology. Journal Diabetes Research. 2016;2016, article 5263798:1–13. doi: 10.1155/2016/5263798.
    1. Green J., Yurdagul A., Jr., McInnis M. C., Albert P., Orr A. W. Flow patterns regulate hyperglycemia-induced subendothelial matrix remodeling during early atherogenesis. Atherosclerosis. 2014;232(2):277–284. doi: 10.1016/j.atherosclerosis.2013.11.052.
    1. Lacolley P., Regnault V., Nicoletti A., Li Z., Michel J. B. The vascular smooth muscle cell in arterial pathology: a cell that can take on multiple roles. Cardiovascular Research. 2012;95(2):194–204. doi: 10.1093/cvr/cvs135.
    1. Simó R., Hernández C., Hernández C. Neurodegeneration in the diabetic eye: new insights and therapeutic perspectives. Trends in Endocrinology and Metabolism. 2014;25(1):23–33. doi: 10.1016/j.tem.2013.09.005.
    1. Straznicky N. E., Grima M. T., Eikelis N., et al. The effects of weight loss versus weight loss maintenance on sympathetic nervous system activity and metabolic syndrome components. The Journal of Clinical Endocrinology and Metabolism. 2011;96(3):E503–E508. doi: 10.1210/jc.2010-2204.
    1. Thorp A. A., Schlaich M. P. Relevance of sympathetic nervous system activation in obesity and metabolic syndrome. Journal Diabetes Research. 2015;2015, article 341583:1–11. doi: 10.1155/2015/341583.
    1. Matthews V. B., Elliot R. H., Rudnicka C., Hricova J., Herat L., Schlaich M. P. Role of the sympathetic nervous system in regulation of the sodium glucose cotransporter 2. Journal of Hypertension. 2017;35(10):2059–2068. doi: 10.1097/HJH.0000000000001434.
    1. Herat L. Y., Matthews V. B., Rakoczy P. E., Carnagarin R., Schlaich M. Focusing on sodium glucose cotransporter-2 and the sympathetic nervous system: potential impact in diabetic retinopathy. International Journal of Endocrinology. 2018;2018:8. doi: 10.1155/2018/9254126.9254126

Source: PubMed

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