SGLT2 Inhibitors: A Noval Therapuetic Agent in the Treatment of Diabetic Kidney Disease
Sodium Glucose Co-transporter2 inhibitors are one of the latest anti diabetic drugs that are approved by USFDA. It include Dapagliflozin, Canagliflozin , Ipragliflozin,Empagliflozin, Tofogliflozin,and Luscogliflozin. They act by inhibiting tubular reabsorption of glucose in kidney and increasing urinary excretion of glucose. SGLT2 inhibitors reduce the workload of the proximal tubules and improve tubulointerstitial hypoxia, and allow fibroblasts to start normal erythropoietin production, and thereby exhibit renoprotection .These drugs have beneficial role in the reduction of HbA1c, cardiovascular risk factors and proteinuria. Use of SGLT2 inhibitor is contraindicated in patients with estimated GFR less than 30 mL/min or End stage renal failure Genitourinary infections are most common adverse effects associated with these drugs, predominantly in female.
Keywords: Diabetes Mellitus, Diabetic Nephropathy, Hyperfiltration, Natriuresis, Macroalbuminuria, Endothelial dysfunction, Intraglomerular filtration, ketoacidosis, amputations, apoptosis
2) Cooper ME. Pathogenesis, prevention, and treatment of diabetic nephropathy. The Lancet. 1998 Jul 18; 352(9123):213-9
3) Rieg T, Masuda T, Gerasimova M, Mayoux E, Platt K, Powell DR, Thomson SC, Koepsell H, Vallon V. Increase in SGLT1-mediated transport explains renal glucose reabsorption during genetic and pharmacological SGLT2 inhibition in euglycemia. American Journal of Physiology-Renal Physiology. 2013 Nov 13; 306(2):F188-93.
4) Kasichayanula S, Liu X, LaCreta F, Griffen SC, Boulton DW. Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clinical pharmacokinetics. 2014 Jan 1; 53(1):17-27.
5) Devineni D, Curtin CR, Polidori D, Gutierrez MJ, Murphy J, Rusch S, Rothenberg PL. Pharmacokinetics and pharmacodynamics of canagliflozin, a sodium glucose co‐transporter 2 inhibitor, in subjects with type 2 diabetes mellitus. The Journal of Clinical Pharmacology. 2013 Jun; 53(6):601-10
6) Macha S, Mattheus M, Halabi A, Pinnetti S, Woerle HJ, Broedl UC. Pharmacokinetics, pharmacodynamics and safety of empagliflozin, a sodium glucose cotransporter2 (SGLT2) inhibitor, in subjects with renal impairment. Diabetes, Obesity and Metabolism. 2014 Mar; 16(3):215-22
7) Zhang W, Krauwinkel WJ, Keirns J, Townsend RW, Lasseter KC, Plumb L, Kadokura T, Ushigome F, Smulders R. The effect of moderate hepatic impairment on the pharmacokinetics of ipragliflozin, a novel sodium glucose co-transporter 2 (SGLT2) inhibitor. Clinical drug investigation. 2013 Jul 1; 33(7):489-96.
8) Schwab D, Portron A, Backholer Z, Lausecker B, Kawashima K. A novel double-tracer technique to characterize absorption, distribution, metabolism and excretion (ADME) of [14 C] tofogliflozin after oral administration and concomitant intravenous microdose administration of [13 C] tofogliflozin in humans.Clinical pharmacokinetics. 2013 Jun 1; 52(6):463-73
9) Scheen AJ. SGLT2 inhibitors: benefit/risk balance. Current diabetes reports. 2016 Oct 1; 16(10):92.
10) Lupsa BC, Inzucchi SE. Use of SGLT2 inhibitors in type 2 diabetes: weighing the risks and benefits. Diabetologia. 2018 Oct 1; 61(10):2118-25.
11) Verma S, McMurray JJ. SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review. Diabetologia. 2018 Oct 1; 61(10):2108-17.
12) Foote C, Perkovic V, Neal B. Effects of SGLT2 inhibitors on cardiovascular outcomes. Diabetes and Vascular Disease Research. 2012 Apr; 9(2):117-23.
13) Ryan PB, Buse JB, Schuemie MJ, DeFalco F, Yuan Z, Stang PE, Berlin JA, Rosenthal N. Comparative effectiveness of canagliflozin, SGLT2 inhibitors and non‐SGLT2 inhibitors on the risk of hospitalization for heart failure and amputation in patients with type 2 diabetes mellitus: a real‐world meta‐analysis of 4 observational databases (OBSERVE‐4D). Diabetes, Obesity and Metabolism. 2018 Nov; 20(11):2585-97..
14) Vallon V, Thomson SC. Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition. Diabetologia. 2017 Feb 1; 60(2):215-25.
15) Chino Y, Samukawa Y, Sakai S, Nakai Y, Yamaguchi JI, Nakanishi T, Tamai I. SGLT2 inhibitor lowers serum uric acid through alteration of uric acid transport activity in renal tubule by increased glycosuria. Biopharmaceutics& drug disposition. 2014 Oct; 35(7):391-404.
16) Schernthaner G, Mogensen CE, Schernthaner GH. The effects of GLP-1 analogues, DPP-4 inhibitors and SGLT2 inhibitors on the renal system.Diabetes and Vascular Disease Research. 2014 Sep; 11(5):306-23
17)Cooper ME. Pathogenesis, prevention, and treatment of diabetic nephropathy.The Lancet. 1998 Jul 18;352(9123):213-9
18) Taylor SI, Blau JE, Rother KI. SGLT2 inhibitors may predispose to ketoacidosis. The Journal of Clinical Endocrinology & Metabolism. 2015 Aug 1; 100(8):2849-52.
19) Rosenstock J, Ferrannini E. Euglycemic diabetic ketoacidosis: a predictable, detectable, and preventable safety concern with SGLT2 inhibitors. Diabetes care. 2015 Sep 1; 38(9):1638-42.
20) Ogawa W, Sakaguchi K. Euglycemic diabetic ketoacidosis induced by SGLT2 inhibitors: possible mechanism and contributing factors. Journal of diabetes investigation. 2016 Mar; 7(2):135.
21) Halimi S, Verges B. Adverse effects and safety of SGLT-2 inhibitors. Diabetes & metabolism. 2014 Dec 1; 40(6):S28-34.
22) Scheen AJ. Drug–drug interactions with sodium-glucose cotransporters type 2 (SGLT2) inhibitors, new oral glucose-lowering agents for the management of type 2 diabetes mellitus. Clinical pharmacokinetics. 2014 Apr 1; 53(4):295-304.
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