**Author details**

data regarding the long-term effects of SGLT2 inhibitors on bone metabolism, making room

There have been reports regarding several cases of bladder cancer and breast cancer, in subjects with T2DM receiving treatment with dapagliflozin [58]. Trials with large numbers of patients with different SGLT2 inhibitors are required to assess any associated increased risks of breast

Theoretical safety and tolerability concerns also include impairment in renal function [54]. Although, until now, there are no data indicating that the SLGT2 inhibitors would determine or be responsible for deterioration of renal function, the few clinical studies investigating these drugs have relatively short duration (6-12 months). Moreover, several authors are speculating that SGLT2 inhibitors may play an important role in preventing diabetic nephropathy. First, improved glycaemic control decreases the risk of diabetic nephropathy and other diabetic complications [40]. Second, by increasing the quantity of sodium in the juxtaglomerular apparatus, the use of SGLT2 inhibitors may determine a protective effect on the kidney,

In T2DM, the high quantity of glucose and sodium absorbed in the proximal tubule reduces the quantity of sodium to be delivered to the juxtaglomerular apparatus. Thus, the glomerulotubular feedback reflex is activated; this leads to high renal plasma flow, increased intraglomerular pressure and elevated GFR. All these processes can induce normal salt delivery to the juxtaglomerular apparatus; however this can result in increased intra-glomerular pressure. All these alterations in renal hemodynamic lead to renal hypertrophy and eventually the result is represented by diabetic nephropathy [59]. SGLT2 inhibitors may prevent diabetic nephrop‐ athy by inhibiting the glomerulo-tubular feedback reflex and, therefore increasing sodium delivery to the distal nephron [1]. Nevertheless, this therapy is contraindicated in patients with

mL/min/1.73 m2 [60]. New clinical trials are expected to evaluate the efficacy and safety of

The pathogenesis of type 2 diabetes combines numerous defects in many tissues. Therefore, there is no single antidiabetic drug that can compensate all the metabolic disturbances, and a good treatment for diabetes will require the use of multiple drugs in combination. Having a unique pharmacokinetic and a special mechanism of action, the SGLT2 inhibitors can be used not only as monotherapy [61] but also in combination with currently available antidiabetic

Although not traditionally discussed, the kidneys play a very important role in maintaining glucose homeostasis by gluconeogenesis and glucose reabsorption, the latter being mediated by active (SGLT) and passive (GLUT) transporters. Only recently, excessive renal glucose reabsorption was taken into consideration regarding its importance in the physiopathology of

and must be used at lower doses at eGFRs of 45-60

for other clinical studies on this important issue.

or bladder cancer [3].

16 Treatment of Type 2 Diabetes

independently of glucose decreased.

estimated GFR (eGFR) <45 mL/min/1.73 m2

SGLT2 inhibitors.

agents [62,63].

**7. Conclusions**

Maria Mota1\*, Eugen Mota2 and Ilie-Robert Dinu2

\*Address all correspondence to: mmota53@yahoo.com

1 Department of Diabetes, Nutrition, Metabolic Diseases, University of Medicine and Pharmacy Craiova, Romania

2 Department of Nephrology, University of Medicine and Pharmacy Craiova, Romania

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