Extraglycemic Effects of SGLT2 Inhibitors: A Review of the Evidence

Abstract

Patients with type 2 diabetes (T2D) are often overweight/obese and affected by arterial hypertension, dyslipidaemia, and have high serum levels of uric acid. Moreover, T2D patient have a higher risk of developing cardiovascular or renal complications, which are leading causes of morbidity and mortality in this population. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a new class of glucose-lowering medications that block the reabsorption of glucose in the kidney, thereby increasing urinary glucose excretion, and lowering blood glucose levels. The beneficial effects of SGLT2 inhibition extend beyond glycaemic control, and include improvement in blood pressure, body weight, uric acid concentrations, liver steatosis, oxidative stress, and inflammation. In dedicated cardiovascular outcome trials, SGLT2i treatment was associated with a significant reduction in the rate of cardiovascular events and renal endpoints. In this review, we summarize the evidence for extra-glycemic effects of SGLT2i and the potential mechanisms driving cardiorenal protection exerted by this class of medications.

Keywords: cardiovascular effects; renal effects; review; sodium-glucose cotransporter-2 inhibitors; type 2 diabetes.

Figure 1

Potential mechanisms for the cardio-/nephroprotective effects of SGLT2i. The effects observed in large clinical trials are shown in the green box, those resulted from studies with a small number of patients or in animal models are shown in the red box.