Sodium Glucose Cotransporter 2 Inhibitors in the Treatment of Diabetes: Cardiovascular and Kidney Effects, Potential Mechanisms and Clinical Applications.

Sodium Glucose Cotransporter 2 Inhibitors in the Treatment of Diabetes: Cardiovascular and Kidney Effects, Potential Mechanisms and Clinical Applications. Circulation. 2016 Jul 28; Authors: Heerspink HJ, Perkins BA, Fitchett DH, Husain M, Cherney DZ Abstract Sodium glucose co-transporter-2 (SGLT2) inhibitors, including empagliflozin, dapagliflozin and canagliflozin, are now widely approved anti-hyperglycemic therapies. Due to their unique glycosuric mechanism, SGLT2 inhibitors also reduce weight. Perhaps more importantly are osmotic diuretic and natriuretic effects contributing to plasma volume contraction, and decreases in systolic and diastolic blood pressures (BP) by 4-6/1-2 mmHg, respectively, which may underlie cardiovascular and kidney benefits. SGLT2 inhibition is also associated with an acute, dose-dependent reduction in eGFR by ~5 ml/min/1.73m(2) and ~30-40% reduction in albuminuria. These effects mirror pre-clinical observations suggesting that proximal tubular natriuresis activates renal tubuloglomerular feedback through increased macula densa sodium and chloride delivery, leading to afferent vasoconstriction. On the basis of reduced glomerular filtration, glycosuric and weight loss effects are attenuated in patients with chronic kidney disease (CKD, eGFR <60 ml/min/1.73m(2)). In contrast, BP lowering, eGFR and albuminuric effects are preserved, and perhaps exaggerated in CKD. With regards to long term clinical outcomes...
Source: Circulation - Category: Cardiology Authors: Tags: Circulation Source Type: research