Sodium glucose co-transporter 2 (SGLT2) inhibitors exhibit diuretic activity, which is a possible mechanism underlying the cardiovascular benefit of these inhibitors. However, the osmotic diuresis-induced increase in urine volume, and the risk of dehydration have been of concern with SGLT2 inhibitor treatment. This study aimed to investigate the mechanism underlying SGLT2 inhibitor canagliflozin-induced diuresis in Japanese type 2 diabetes mellitus (T2DM) patients.
Thirteen T2DM patients received a daily oral dose of 100 mg canagliflozin before breakfast for 6 days. Blood and urine samples were collected at predetermined time points. The primary endpoint was evaluation of correlations between changes from baseline in urine volume and factors that are known to affect urine volume and between actual urine volume and these factors.
Canagliflozin transiently increased urine volume and urinary sodium excretion on Day 1 with a return to baseline levels thereafter. Canagliflozin administration increased urinary glucose excretion, which was sustained during repeated-dose administration. Plasma atrial natriuretic peptide (ANP) and N-terminal pro-b-type natriuretic peptide (NT-proBNP) levels decreased, while plasma renin activity increased. On Day 1 of treatment, changes in sodium and potassium excretion were closely correlated with changes in urine output. A post hoc multiple regression analysis showed changes in sodium excretion and water intake as factors that affected urine volume change at Day 1. Furthermore, relative to that at baseline, canagliflozin decreased blood glucose throughout the day and increased plasma total GLP-1 after breakfast.
Canagliflozin induced transient sodium excretion and did not induce water intake at Day 1; hence, natriuresis rather than glucose-induced osmotic diuresis may be a major factor involved in the canagliflozin-induced transient increase in urine output. In addition, canagliflozin decreased plasma ANP and NT-proBNP levels and increased plasma renin activity, which may be a compensatory mechanism for sodium retention, leading to subsequent urine output recovery.
Mitsubishi Tanabe Pharma Corporation.
Supplementary material 1 (DOCX 270 kb)12325_2016_457_MOESM1_ESM.docx
Lorber D. Importance of cardiovascular disease risk management in patients with type 2 diabetes mellitus. Diabetes, Metab Syndr Obes. 2014;7:169–83. CrossRef
Ghosh RK, Bandyopadhyay D, Hajra A, Biswas M, Gupta A. Cardiovascular outcomes of sodium-glucose cotransporter 2 inhibitors: a comprehensive review of clinical and preclinical studies. Int J Cardiol. 2016;1(212):29–36. CrossRef
Takeuchi T, Dohi K, Omori T, Moriwaki K, Sato Y, Nakamori S, et al. Diuretic effects of sodium-glucose cotransporter 2 inhibitor in patients with type 2 diabetes mellitus and heart failure. Int J Cardiol. 2015;15(201):1–3. CrossRef
Rennke H, Denker B. Renal pathophysiology: the essentials. 4th ed. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins; 2014.
Piuhola J, Kerkela R, Keenan JI, Hampton MB, Richards AM, Pemberton CJ. Direct cardiac actions of erythropoietin (EPO): effects on cardiac contractility, BNP secretion and ischaemia/reperfusion injury. Clin Sci (Lond). 2008;114(4):293–304. CrossRef
Polidori D, Sha S, Mudaliar S, Ciaraldi TP, Ghosh A, Vaccaro N, et al. Canagliflozin lowers postprandial glucose and insulin by delaying intestinal glucose absorption in addition to increasing urinary glucose excretion: results of a randomized, placebo-controlled study. Diabetes Care. 2013;36(8):2154–61. CrossRefPubMedPubMedCentral
Kinoshita S, Kondo K. Evaluation of pharmacokinetic and pharmacodynamic interactions of canagliflozin and teneligliptin in Japanese healthy male volunteers. Expert Opin Drug Metab Toxicol. 2015;11(1):7–14. PubMed
- Factors Affecting Canagliflozin-Induced Transient Urine Volume Increase in Patients with Type 2 Diabetes Mellitus
- Springer Healthcare
Neu im Fachgebiet Innere Medizin
Meistgelesene Bücher aus der Inneren Medizin
Mail Icon II