Sodium-glucose cotransport inhibitors: mechanisms, metabolic effects and implications for the treatment of diabetic patients with chronic kidney disease.

Publisher: Oxford University Press Country of Publication: England NLM ID: 8706402 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1460-2385 (Electronic) Linking ISSN: 09310509 NLM ISO Abbreviation: Nephrol Dial Transplant Subsets: MEDLINE

Publication: Oxford : Oxford University Press
Original Publication: [Berlin ; New York, NY] : Springer International, [c1986-

Sodium-Glucose Transporter 2 Inhibitors*; Diabetes Mellitus, Type 2/*drug therapy ; Diabetes Mellitus, Type 2/*metabolism ; Hypoglycemic Agents/*therapeutic use ; Renal Insufficiency, Chronic/*drug therapy ; Renal Insufficiency, Chronic/*metabolism; Animals ; Humans

Remarkable progress has been achieved in the field of diabetes with the development of incretin analogues, dipeptidyl peptidase IV inhibitors and novel insulin analogues; nevertheless, there is an unmet need for additional therapeutic options. Individualization of HbA1c target levels is a recent progress within the field. Approximately 50% of diabetics do not reach a previously aspired treatment goal of glycosylated HbA1 levels below 7% and often face a vicious circle with accelerated weight gain. Current antidiabetic therapeutics mainly target the decline in insulin secretion and ameliorate insulin resistance. In this regard a new generation of drugs, denoted gliflozines, that specifically interfere with sodium-glucose cotransporters (SGLT)-2 and exhibit a favourable impact on glucose metabolism in patients with type 2 diabetes are emerging as hopeful avenues. The resultant negative energy balance caused by glucosuria results in long-term weight losses, significantly reduced HbA1c levels approximating 0.5-1.0% and may in addition exert beneficial effects on blood pressure, reactive oxygen products and inflammatory mediators. Recent studies indicate improvement in β-cell glucose sensitivity and insulin sensitivity in patients treated with gliflozines, a decrease in tissue glucose disposal and interestingly an increase in endogenous glucose production. The list of side effects observed under SGLT2 inhibition includes increased rates of genitourinary infections, balanitis, vulvovaginitis, hypotensive episodes and acute deterioration of kidney function. Main questions towards the safety profile are still unanswered given that long-term clinical outcome data with SGLT2 inhibition are lacking and the cardiovascular safety profile is under scrutiny in large trials. Thus, the successful development of selective SGLT2 inhibitors for therapeutic use in diabetics has a huge potential to meet patients' needs. However, it awaits quick results from clinical trials with meaningful clinical endpoints.
(© The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Keywords: diabetes; gliflozines; glucosuria; inflammation; nephropathy

0 (Hypoglycemic Agents)
0 (Sodium-Glucose Transporter 2 Inhibitors)

Date Created: 20140919 Date Completed: 20160216 Latest Revision: 20181202

20240628

10.1093/ndt/gfu299

25230708