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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. The 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. 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.

Recent evidence link SGLT2 inhibition with reduction of cardiovascular events in type 2 diabetes (EMPA-REG OUTCOME study) and markers of kidney damage (that is micro- and macroalbuminuria). Notably the rate of side effects observed under SGLT2 inhibition was low and discerned by some trials, however markedly higher in earlier trials. 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. Hemodynamic effects by SGLT2 inhibition are the most likely the reason for cardio- and renoprotective effects. Thus, selective SGLT2 inhibitors have a huge potential to meet patients’ needs which will be covered in the lecture.

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