SGLT-2 inhibitors

a novelty in the treatment of type 2 diabetes

  • Mojca Lunder Department of Endocrinology, Diabetes and Metabolic Diseases, Division of Internal Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia
  • Miodrag Janić Department of Vascular Diseases, Division of Internal Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia
  • Mišo Šabovič Department of Vascular Diseases, Division of Internal Medicine, University Medical Centre Ljubljana, Ljubljana
  • Andrej Janež Klinični oddelek za endokrinologijo, diabetes in presnovne bolezni, Univerzitetni klinični center Ljubljana
Keywords: SGLT-2 inhibitors, glycaemia control, blood pressure, cardiovascular diseases, undesired side effects


Sodium glucose co-transporter-2 (SGLT-2) inhibitors are the newest group of drugs for the treatment of diabetes mellitus type 2, which have been in clinical use for the last few years. They act in the proximal renal tubules by reducing the glucose reabsorption, the glucose then being excreted in the urine. Consequently, by decreasing blood glucose levels, they have a favourable effect on the glycaemia control and importantly do not increase the risk of hypoglycaemia. SGLT-2 inhibitors also possess favourable metabolic effects, especially on weight reduction, blood pressure reduction and serum uric acid level reduction. They also slow down the progression of the diabetic kidney disease. For some SGLT-2 inhibitors it was also shown that they exert beneficial effects on the cardiovascular system by reducing cardiovascular events and complications through yet unknown mechanisms, which are subject of intensive study. SGLT-2 inhibitors rarely cause serious side effects. The present manuscript describes the mechanism of action of SGLT-2 inhibitors, their effect on the glycaemia control, metabolic effects, effects on the incidence of cardiovascular disease, the most common side effects and prescribing restrictions for SGLT-2 inhibitors in Slovenia.


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Vallianou NG, Geladari E, Kazazis CE. SGLT-2 inhibitors: their pleiotropic properties. Diabetes Metab Syndr. 2017 Oct - Dec;11(4):311–5. PMID:28011230

Diabetes Atlas ID. - 8th Edition 2017 [Available from:

Storgaard H, Gluud LL, Bennett C, Grøndahl MF, Christensen MB, Knop FK, et al. Benefits and Harms of Sodium-Glucose Co-Transporter 2 Inhibitors in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis. PLoS One. 2016 Nov;11(11):e0166125. PMID:27835680

Ivo-Dos-Santos J, Campos DL, Galvão-Castro B. Patterns of serologic response to human immunodeficiency virus type 1 (HIV-1) in Brazilians with different clinical forms of HIV infection. Mem Inst Oswaldo Cruz. 1989 Jan-Mar;84(1):9–11. PMID:2319954

Kalra S, Singh V, Nagrale D. Sodium-Glucose Cotransporter-2 Inhibition and the Glomerulus: A Review. Adv Ther. 2016 Sep;33(9):1502–18. PMID:27423646

Kalra S. Sodium Glucose Co-Transporter-2 (SGLT2) Inhibitors: A Review of Their Basic and Clinical Pharmacology. Diabetes Ther. 2014 Dec;5(2):355–66. PMID:25424969

Lioudaki E, Androulakis ES, Whyte M, Stylianou KG, Daphnis EK, Ganotakis ES. The Effect of Sodium-Glucose Co-transporter-2 (SGLT-2) Inhibitors on Cardiometabolic Profile; Beyond the Hypoglycaemic Action. Cardiovasc Drugs Ther. 2017 Apr;31(2):215–25. PMID:28444472

Martens P, Mathieu C, Verbrugge FH. Promise of SGLT2 Inhibitors in Heart Failure: diabetes and Beyond. Curr Treat Options Cardiovasc Med. 2017 Mar;19(3):23. PMID:28299616

Zinman B, Lachin JM, Inzucchi SE. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2016 Mar;374(11):1094. PMID:26981940

Farahani P. Non-severe Hypoglycemia Risk Difference between Sulfonylurea and Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2-I) as an Add-On to Metformin in Randomized Controlled Trials. J Popul Ther Clin Pharmacol. 2017 May;24(2):e32–40. PMID:28594482

Cai X, Yang W, Gao X, Chen Y, Zhou L, Zhang S, et al. The Association Between the Dosage of SGLT2 Inhibitor and Weight Reduction in Type 2 Diabetes Patients: A Meta-Analysis. Obesity (Silver Spring). 2018 Jan;26(1):70–80. PMID:29165885

Ahmadieh H, Azar S. Effects of Sodium Glucose Cotransporter-2 Inhibitors on Serum Uric Acid in Type 2 Diabetes Mellitus. Diabetes Technol Ther. 2017 Sep;19(9):507–12. PMID:28749169

Shyangdan DS, Uthman OA, Waugh N. SGLT-2 receptor inhibitors for treating patients with type 2 diabetes mellitus: a systematic review and network meta-analysis. BMJ Open. 2016 Feb;6(2):e009417. PMID:26911584

Cherney DZ, Perkins BA, Soleymanlou N, Har R, Fagan N, Johansen OE, et al. The effect of empagliflozin on arterial stiffness and heart rate variability in subjects with uncomplicated type 1 diabetes mellitus. Cardiovasc Diabetol. 2014 Jan;13(1):28. PMID:24475922

Fioretto P, Zambon A, Rossato M, Busetto L, Vettor R. SGLT2 Inhibitors and the Diabetic Kidney. Diabetes Care. 2016 Aug;39 Suppl 2:S165–71. PMID:27440829

Perrone-Filardi P, Avogaro A, Bonora E, Colivicchi F, Fioretto P, Maggioni AP, et al. Mechanisms linking empagliflozin to cardiovascular and renal protection. Int J Cardiol. 2017 Aug;241:450–6. PMID:28395981

Rastogi A, Bhansali A. SGLT2 Inhibitors Through the Windows of EMPA-REG and CANVAS Trials: A Review. Diabetes Ther. 2017 Dec;8(6):1245–51. PMID:29076040

Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al.; EMPA-REG OUTCOME Investigators. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015 Nov;373(22):2117–28. PMID:26378978

Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, et al.; CANVAS Program Collaborative Group. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017 Aug;377(7):644–57. PMID:28605608

Filippatos TD, Tsimihodimos V, Liamis G, Elisaf MS. SGLT2 inhibitors-induced electrolyte abnormalities: an analysis of the associated mechanisms. Diabetes Metab Syndr. 2018 Jan - Mar;12(1):59–63. PMID:28826578

Lytvyn Y, Bjornstad P, Udell JA, Lovshin JA, Cherney DZ. Sodium Glucose Cotransporter-2 Inhibition in Heart Failure: Potential Mechanisms, Clinical Applications, and Summary of Clinical Trials. Circulation. 2017 Oct;136(17):1643–58. PMID:29061576

Rosenstock J, Ferrannini E. Euglycemic Diabetic Ketoacidosis: A Predictable, Detectable, and Preventable Safety Concern With SGLT2 Inhibitors. Diabetes Care. 2015 Sep;38(9):1638–42. PMID:26294774

Goldenberg RM, Berard LD, Cheng AY, Gilbert JD, Verma S, Woo VC, et al. SGLT2 Inhibitor-associated Diabetic Ketoacidosis: Clinical Review and Recommendations for Prevention and Diagnosis. Clin Ther. 2016;38(12):2654–64 e1.

Handelsman Y, Henry RR, Bloomgarden ZT, Dagogo-Jack S, DeFronzo RA, Einhorn D, et al. American Association of Clinical Endocrinologists and American College of Endocrinology Position Statement on the Association of Sglt-2 Inhibitors and Diabetic Ketoacidosis. Endocr Pract. 2016 Jun;22(6):753–62. PMID:27082665

Scheen AJ. Pharmacodynamics, efficacy and safety of sodium-glucose co-transporter type 2 (SGLT2) inhibitors for the treatment of type 2 diabetes mellitus. Drugs. 2015 Jan;75(1):33–59. PMID:25488697

Zaletel J, Ravnik Oblak M, editors. Slovenske smernice za klinično obravnavo sladkorne bolezni tipa 2. 3 ed. Ljubljana: Klinični oddelek za endokrinologijo, diabetes in presnovne bolezni, Interna klinika UKC Ljubljana in Klinični oddelek za endokrinologijo, diabetes in bolezni presnove, Pediatrična klinika Ljubljana; 2016.

How to Cite
Lunder M, Janić M, Šabovič M, Janež A. SGLT-2 inhibitors. ZdravVestn [Internet]. 28Oct.2018 [cited 20Jul.2019];87(9-10):493-06. Available from:
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