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SIRT1 gene polymorphisms have been linked with an increased risk of diabetic nephropathy in several epidemiological studies. Importantly, there is an inverse relationship between the activity of SGLT2 and signaling through the SIRT1/PGC-1α/FGF21 pathway, and SGLT2 inhibition leads to activation of these ketogenic nutrient deprivation sensors. Therefore, activation of SIRT1/PGC-1α/FGF21 may explain the effect of SGLT2 inhibitors not only to promote ketogenesis, but also to preserve renal function in type 2 diabetes.Mathematical models a
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