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SGLT 2 inhibitors: Antidiabetic agents with promising effects beyond glucose control

Year 2020, , 1 - 4, 29.01.2020
https://doi.org/10.46310/tjim.674514

Abstract

Type 2 diabetes mellitus is a growing public health problem worldwide. It has a close relation with metabolic problems like obesity, hypertension, dyslipidemia and atherosclerotic cardiovascular diseases. There are different antidiabetic agents being used in the treatment of diabetes mellitus with different mechanisms of action and a patient centered approach is required when choosing the appropriate treatment option. Sodium-glucose cotransporter (SGLT) 2 inhibitors also called glucoretics or gliflozins are members of a relatively new group of antidiabetic agents with promising cardioprotective and renoprotective effects beyond their glucose lowering efficacies.

References

  • The Society of Endocrinology and Metabolism of Turkey, Clinical Practice Guideline for Diagnosis, Treatment and Follow-up of Diabetes Mellitus and Its Complications – 2019. English Version of the 12th Ed. Ankara: Miki Matbaacılık; 2019: 1-268.
  • American Diabetes Association. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2020. Diabetes Care. 2020;43(Suppl 1):S98-S110. doi: 10.2337/dc20-S009.
  • Lioudaki E, Whyte M, Androulakis ES, Stylianou KG, Daphnis EK, Ganotakis ES. Renal Effects of SGLT-2 Inhibitors and Other Anti-diabetic Drugs: Clinical Relevance and Potential Risks. Clin Pharmacol Ther. 2017;102(3):470-480. doi: 10.1002/cpt.731.
  • Vallon V, Thomson SC. Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition. Diabetologia. 2017;60(2):215-225. doi: 10.1007/s00125-016-4157-3.
  • Calapkulu M, Cander S, Gul OO, Ersoy C. Lipid profile in type 2 diabetic patients with new dapagliflozin treatment; actual clinical experience data of six months retrospective lipid profile from single center. Diabetes Metab Syndr. 2019;13(2):1031-1034. doi: 10.1016/j.dsx.2019.01.016.
  • Ferrannini E, Muscelli E, Frascerra S, Baldi S, Mari A, Heise T, Broedl UC, Woerle HJ. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest. 2014;124(2):499-508. doi: 10.1172/JCI72227.
  • Bolinder J, Ljunggren Ö, Kullberg J, Johansson L, Wilding J, Langkilde AM, Sugg J, Parikh S. Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab. 2012;97(3):1020-31. doi: 10.1210/jc.2011-2260.
  • Bolinder J, Ljunggren Ö, Johansson L, Wilding J, Langkilde AM, Sjöström CD, Sugg J, Parikh S. Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes Obes Metab. 2014;16(2):159-69. doi: 10.1111/dom.12189.
  • Monami M, Nardini C, Mannucci E. Efficacy and safety of sodium glucose co-transport-2 inhibitors in type 2 diabetes: a meta-analysis of randomized clinical trials. Diabetes Obes Metab. 2014;16(5):457-66. doi: 10.1111/dom.12244.
  • Guthrie R. Canagliflozin and cardiovascular and renal events in type 2 diabetes. Postgrad Med. 2018;130(2):149-153. doi: 10.1080/00325481.2018.1423852.
  • Lehrke M. SGLT2 Inhibition: Changing What Fuels the Heart. J Am Coll Cardiol. 2019;73(15):1945-1947. doi: 10.1016/j.jacc.2019.02.023.
  • Chino Y, Samukawa Y, Sakai S, Nakai Y, Yamaguchi J, Nakanishi T, Tamai I. SGLT2 inhibitor lowers serum uric acid through alteration of uric acid transport activity in renal tubule by increased glycosuria. Biopharm Drug Dispos. 2014;35(7):391-404. doi: 10.1002/bdd.1909.
  • Magee GM, Bilous RW, Cardwell CR, Hunter SJ, Kee F, Fogarty DG. Is hyperfiltration associated with the future risk of developing diabetic nephropathy? A meta-analysis. Diabetologia. 2009;52(4):691-7. doi: 10.1007/s00125-009-1268-0.
  • Cherney DZ, Perkins BA, Soleymanlou N, Maione M, Lai V, Lee A, Fagan NM, Woerle HJ, Johansen OE, Broedl UC, von Eynatten M. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus. Circulation. 2014;129(5):587-97. doi: 10.1161/CIRCULATIONAHA.113.005081.
  • Heerspink HJ, Desai M, Jardine M, Balis D, Meininger G, Perkovic V.Canagliflozin Slows Progression of Renal Function Decline Independently of Glycemic Effects. J Am Soc Nephrol. 2017;28(1):368-375. doi: 10.1681/ASN.2016030278.
  • van Bommel EJ, Muskiet MH, Tonneijck L, Kramer MH, Nieuwdorp M, van Raalte DH. SGLT2 Inhibition in the Diabetic Kidney-From Mechanisms to Clinical Outcome. Clin J Am Soc Nephrol. 2017;12(4):700-710. doi: 10.2215/CJN.06080616.
  • LiverTox: Clinical and Research Information on Drug-Induced Liver Injury, SGLT-2 Inhibitors, nlm.ncbi.www.nih.gov › books › NBK548289
  • Washburn WN, Poucher SM. Differentiating sodium-glucose co-transporter-2 inhibitors in development for the treatment of type 2 diabetes mellitus. Expert Opin Investig Drugs. 2013;22(4):463-86. doi: 10.1517/13543784.2013.774372.
  • Vasilakou D, Karagiannis T, Athanasiadou E, Mainou M, Liakos A, Bekiari E, Sarigianni M, Matthews DR, Tsapas A. Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med. 2013;159(4):262-74. doi: 10.7326/0003-4819-159-4-201308200-00007.
  • Musso G, Gambino R, Cassader M, Pagano G. A novel approach to control hyperglycemia in type 2 diabetes: sodium glucose co-transport (SGLT) inhibitors: systematic review and meta-analysis of randomized trials. Ann Med. 2012;44(4):375-93. doi: 10.3109/07853890.2011.560181.
  • Dagogo-Jack S, Liu J, Eldor R, Amorin G, Johnson J, Hille D, Liao Y, Huyck S, Golm G, Terra SG, Mancuso JP, Engel SS, Lauring B. Efficacy and safety of the addition of ertugliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sitagliptin: The VERTIS SITA2 placebo-controlled randomized study. Diabetes Obes Metab. 2018;20(3):530-540. doi: 10.1111/dom.13116.
  • Liu XY, Zhang N, Chen R, Zhao JG, Yu P. Efficacy and safety of sodium-glucose cotransporter 2 inhibitors in type 2 diabetes: a meta-analysis of randomized controlled trials for 1 to 2 years. J Diabetes Complications. 2015;29(8):1295-303. doi: 10.1016/j.jdiacomp.2015.07.011.
  • Filippas-Ntekouan S, Filippatos TD, Elisaf MS. SGLT2 inhibitors: are they safe? Postgrad Med. 2018;130(1):72-82. doi: 10.1080/00325481.2018.1394152.
Year 2020, , 1 - 4, 29.01.2020
https://doi.org/10.46310/tjim.674514

Abstract

References

  • The Society of Endocrinology and Metabolism of Turkey, Clinical Practice Guideline for Diagnosis, Treatment and Follow-up of Diabetes Mellitus and Its Complications – 2019. English Version of the 12th Ed. Ankara: Miki Matbaacılık; 2019: 1-268.
  • American Diabetes Association. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2020. Diabetes Care. 2020;43(Suppl 1):S98-S110. doi: 10.2337/dc20-S009.
  • Lioudaki E, Whyte M, Androulakis ES, Stylianou KG, Daphnis EK, Ganotakis ES. Renal Effects of SGLT-2 Inhibitors and Other Anti-diabetic Drugs: Clinical Relevance and Potential Risks. Clin Pharmacol Ther. 2017;102(3):470-480. doi: 10.1002/cpt.731.
  • Vallon V, Thomson SC. Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition. Diabetologia. 2017;60(2):215-225. doi: 10.1007/s00125-016-4157-3.
  • Calapkulu M, Cander S, Gul OO, Ersoy C. Lipid profile in type 2 diabetic patients with new dapagliflozin treatment; actual clinical experience data of six months retrospective lipid profile from single center. Diabetes Metab Syndr. 2019;13(2):1031-1034. doi: 10.1016/j.dsx.2019.01.016.
  • Ferrannini E, Muscelli E, Frascerra S, Baldi S, Mari A, Heise T, Broedl UC, Woerle HJ. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest. 2014;124(2):499-508. doi: 10.1172/JCI72227.
  • Bolinder J, Ljunggren Ö, Kullberg J, Johansson L, Wilding J, Langkilde AM, Sugg J, Parikh S. Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab. 2012;97(3):1020-31. doi: 10.1210/jc.2011-2260.
  • Bolinder J, Ljunggren Ö, Johansson L, Wilding J, Langkilde AM, Sjöström CD, Sugg J, Parikh S. Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes Obes Metab. 2014;16(2):159-69. doi: 10.1111/dom.12189.
  • Monami M, Nardini C, Mannucci E. Efficacy and safety of sodium glucose co-transport-2 inhibitors in type 2 diabetes: a meta-analysis of randomized clinical trials. Diabetes Obes Metab. 2014;16(5):457-66. doi: 10.1111/dom.12244.
  • Guthrie R. Canagliflozin and cardiovascular and renal events in type 2 diabetes. Postgrad Med. 2018;130(2):149-153. doi: 10.1080/00325481.2018.1423852.
  • Lehrke M. SGLT2 Inhibition: Changing What Fuels the Heart. J Am Coll Cardiol. 2019;73(15):1945-1947. doi: 10.1016/j.jacc.2019.02.023.
  • Chino Y, Samukawa Y, Sakai S, Nakai Y, Yamaguchi J, Nakanishi T, Tamai I. SGLT2 inhibitor lowers serum uric acid through alteration of uric acid transport activity in renal tubule by increased glycosuria. Biopharm Drug Dispos. 2014;35(7):391-404. doi: 10.1002/bdd.1909.
  • Magee GM, Bilous RW, Cardwell CR, Hunter SJ, Kee F, Fogarty DG. Is hyperfiltration associated with the future risk of developing diabetic nephropathy? A meta-analysis. Diabetologia. 2009;52(4):691-7. doi: 10.1007/s00125-009-1268-0.
  • Cherney DZ, Perkins BA, Soleymanlou N, Maione M, Lai V, Lee A, Fagan NM, Woerle HJ, Johansen OE, Broedl UC, von Eynatten M. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus. Circulation. 2014;129(5):587-97. doi: 10.1161/CIRCULATIONAHA.113.005081.
  • Heerspink HJ, Desai M, Jardine M, Balis D, Meininger G, Perkovic V.Canagliflozin Slows Progression of Renal Function Decline Independently of Glycemic Effects. J Am Soc Nephrol. 2017;28(1):368-375. doi: 10.1681/ASN.2016030278.
  • van Bommel EJ, Muskiet MH, Tonneijck L, Kramer MH, Nieuwdorp M, van Raalte DH. SGLT2 Inhibition in the Diabetic Kidney-From Mechanisms to Clinical Outcome. Clin J Am Soc Nephrol. 2017;12(4):700-710. doi: 10.2215/CJN.06080616.
  • LiverTox: Clinical and Research Information on Drug-Induced Liver Injury, SGLT-2 Inhibitors, nlm.ncbi.www.nih.gov › books › NBK548289
  • Washburn WN, Poucher SM. Differentiating sodium-glucose co-transporter-2 inhibitors in development for the treatment of type 2 diabetes mellitus. Expert Opin Investig Drugs. 2013;22(4):463-86. doi: 10.1517/13543784.2013.774372.
  • Vasilakou D, Karagiannis T, Athanasiadou E, Mainou M, Liakos A, Bekiari E, Sarigianni M, Matthews DR, Tsapas A. Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med. 2013;159(4):262-74. doi: 10.7326/0003-4819-159-4-201308200-00007.
  • Musso G, Gambino R, Cassader M, Pagano G. A novel approach to control hyperglycemia in type 2 diabetes: sodium glucose co-transport (SGLT) inhibitors: systematic review and meta-analysis of randomized trials. Ann Med. 2012;44(4):375-93. doi: 10.3109/07853890.2011.560181.
  • Dagogo-Jack S, Liu J, Eldor R, Amorin G, Johnson J, Hille D, Liao Y, Huyck S, Golm G, Terra SG, Mancuso JP, Engel SS, Lauring B. Efficacy and safety of the addition of ertugliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sitagliptin: The VERTIS SITA2 placebo-controlled randomized study. Diabetes Obes Metab. 2018;20(3):530-540. doi: 10.1111/dom.13116.
  • Liu XY, Zhang N, Chen R, Zhao JG, Yu P. Efficacy and safety of sodium-glucose cotransporter 2 inhibitors in type 2 diabetes: a meta-analysis of randomized controlled trials for 1 to 2 years. J Diabetes Complications. 2015;29(8):1295-303. doi: 10.1016/j.jdiacomp.2015.07.011.
  • Filippas-Ntekouan S, Filippatos TD, Elisaf MS. SGLT2 inhibitors: are they safe? Postgrad Med. 2018;130(1):72-82. doi: 10.1080/00325481.2018.1394152.
There are 23 citations in total.

Details

Primary Language English
Subjects ​Internal Diseases
Journal Section Editorial
Authors

Canan Ersoy 0000-0003-4510-6282

Publication Date January 29, 2020
Submission Date January 14, 2020
Acceptance Date January 21, 2020
Published in Issue Year 2020

Cite

EndNote Ersoy C (January 1, 2020) SGLT 2 inhibitors: Antidiabetic agents with promising effects beyond glucose control. Turkish Journal of Internal Medicine 2 1 1–4.

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