Department of Internal Medicine, National Hospital Organization Matsumoto Medical Center Matsumoto Hospital, JapanJapan
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Sodium-glucose co-transporter 2 (SGLT2) inhibitors, a new class of anti-diabetic agents, have been recently approved for treatment of type 2 diabetes. It was unexpected that possible adverse effects of SGLT2 inhibitors, including fatal events, were reported frequently soon after the first one was marketed in April 2014 in Japan. In poorly-controlled diabetic patients, pre-existing osmotic diuresis is supposed to be augmented by the administration of SGLT2 inhibitors, possibly leading to an acceleration of their dehydration in spite of amelioration of hyperglycemia. It may be reasonable that not only water but a small amount of salt needs to be supplemented with, if necessary, to prevent plasma volume depletion with salt loss. Otherwise, it seems to be a plausible option for such patients to decrease carbohydrate intake by 50 to 100 g of carbohydrate per day during hyperglycemia, instead of excreting a similar amount of glucose into urine with SGLT2 inhibitors.
Keywords: SGLT2 inhibitors; Glucosuria Osmotic diuresis; Dehydration Carbohydrate intake; Glucosuria; Osmotic diuresis; Dehydration; Carbohydrate in- take
Opinion Administration of Sodium-Glucose Co-transporter * 2 Inhibitors Could Accelerate Dehydration in Corresponding author Yuji Aoki, MD, PhD Department of Internal Medicine Poorly-Controlled Diabetic Patients, Proposing an National Hospital Organization Matsumoto Medical Center Option not to Increase Glucosuria but to Matsumoto Hospital Decrease Carbohydrate Intake during 2-20-30 Minami, Murai Matsumoto 399-8701, Japan Hyperglycemia Tel. 0263 58 4567 Fax: 0263 86 3183 E-mail: yaoki55@nifty.com * Yuji Aoki* Volume 1 : Issue 3 Article Ref. #: 1000DROJ1111 Department of Internal Medicine, National Hospital Organization Matsumoto Medical Center Matsumoto Hospital, Japan Article History th Received: June 25th, 2015 ABSTRACT st Accepted: July 1st, 2015 st Published: July 1st, 2015 Sodium-glucose co-transporter 2 (SGLT2) inhibitors, a new class of anti-diabetic agents, have been recently approved for treatment of type 2 diabetes. It was unexpected that possible adverse effects of SGLT2 inhibitors, including fatal events, were reported frequently Citation soon after the first one was marketed in April 2014 in Japan. In poorly-controlled diabetic Aoki Y, Administration of sodium-glu- patients, pre-existing osmotic diuresis is supposed to be augmented by the administration of cose co-transporter 2 inhibitors could accelerate dehydration in poorly- SGLT2 inhibitors, possibly leading to an acceleration of their dehydration in spite of amelio- controlled diabetic patients, propos- ration of hyperglycemia. It may be reasonable that not only water but a small amount of salt ing an option not to increase glucos- needs to be supplemented with, if necessary, to prevent plasma volume depletion with salt loss. uria but to decrease carbohydrate Otherwise, it seems to be a plausible option for such patients to decrease carbohydrate intake intake during hyperglycemia. Diabe- tes Res Open J. 2015; 1(3): 72-74. by 50 to 100 g of carbohydrate per day during hyperglycemia, instead of excreting a similar doi: 10.17140/DROJ-1-111 amount of glucose into urine with SGLT2 inhibitors. KEYWORDS: SGLT2 inhibitors; Glucosuria; Osmotic diuresis; Dehydration; Carbohydrate in- take.
Sodium-glucose co-transporter 2 (SGLT2) inhibitors, a new class of anti-diabetic agents, have been recently approved for treatment of type 2 diabetes, since dapagliflozin was first approved by the European Medicines Agency in November 2012. SGLT2 inhibitors de- crease hyperglycemia independently of insulin by increasing urinary glucose excretion through the inhibition of glucose reabsorption in the proximal renal tubule. They have some advantages including modest weight loss, low risk of hypoglycemia and mild decrease of blood pres- sure.1 However, it is reported that Canagliflozin cardiovascular assessment study (CANVAS) showed an increase of cardiovascular events during the first 30 days in patients who received canagliflozin,2 the first SGLT2 inhibitor approved in the United States in March 2013. In Japan, six SGLT2 inhibitors have been approved since January 2014. It is a matter of concern that the Japan Diabetes Society announced an alert regarding proper use of SGLT2 inhibitors, twice in June and August 2014. It was unexpected that possible adverse effects of SGLT2 inhibitors were reported frequently soon after the first one was marketed in April 2014. Finally, dehydra- tion, which seemed to be occasionally linked to fatal adverse events, was added as a severe Copyright ©2015 Aoki Y. This is an open ac- adverse effect to a package insert in January 2015. cess article distributed under the Creative Commons Attribution 4.0 Familial renal glucosuria with normoglycemia is often referred to as a natural model International License (CC BY 4.0), which permits unrestricted use, for SGLT2 inhibition. Plasma volume depletion resulting from osmotic diuresis was indicated distribution, and reproduction in by activation of the renin-angiotensin-aldosterone system in cases of severe renal glucosuria any medium, provided the original 2 3,4 (>10 g/1.73m /24h) with a favourable prognosis. Such activation has been shown after the work is properly cited.
administration of empagliflozin, another SGLT2 inhibitor, in type 1 diabetic patients. In line with plasma volume depletion, salt loss is suggested to occur CONFLICTS OF INTEREST 6,7 early after the administration of SGLT2 inhibitors,6,7 reaching to a new balance of total body salt. The diuretic effect of dapa- The author declares that he has no conflicts of interest.
gliflozin causes small but significant increases in urine volume, blood urea nitrogen and hematocrit without an increase in serum