Sodium-glucose cotransporter 2 inhibitors: Potential cardiovascular and mortality benefits

Background: The impact of overt diabetes and poor glycemic control on the risk of cardiovascular disease is well established. Among patients with type 2 diabetes, several studies demonstrated a significant increase in coronary artery disease-related death and cardiovascular events associated with HbA1c levels of greater than 7% compared with lower levels. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are a novel class of anti-diabetic drugs that lower blood glucose levels through the suppression of renal glucose reabsorption thereby promoting renal glucose excretion. Objectives: To summarize data on the potential mechanisms of SGLT-2 inhibition that could exert cardiovascular benefits in patients with diabetes mellitus. Method: We conducted an in-depth literature search of SGLT-2 inhibitors and potential cardiovascular benefits and mechanisms that mediate those effects. Results: In diabetes, expression of the SGLT-2 genes is up-regulated and renal threshold increased, resulting in increased glucose reabsorption from glomerular filtrate, reducing urinary glucose excretion and worsening hyperglycemia. SGLT-2 inhibition should offer potential cardiovascular protection in diabetic patients via attenuating hyperglycemia, blood pressure, body weight, hyperuricemia, and diabetic nephropathy. Conclusion: The initial data of SGLT-2 inhibitors suggest beneficial effects on cardiovascular risk among patients with diabetes mellitus. Several mechanisms are hypothesized to mediate the abovementioned benefits. Future randomized, controlled studies are needed in order to unveil the contribution of each mechanism to these outcomes. © 2018 Bentham Science Publishers

Sodium-glucose cotransporter 2 inhibitors: Impact on body weight and blood pressure compared with other antidiabetic drugs

Background: Sodium-glucose co-transporters 2 inhibitors have emerged as a novel antidiabetic class of drugs offering significant ameliorating effects on a variety of cardiovascular risk factors, secondary to their mechanism of action, including blood pressure and body weight. Objective: The purpose of this article is to discuss available data on the impact of SGLT-2 inhibitors on blood pressure and body weight compared with other available anti-diabetic drugs and to present potential mechanisms mediating these effects. Methods: A comprehensive review of the literature was performed to identify studies examining the effects of SGLT-2 inhibitors on blood pressure and body weight. Results: SGLT-2 inhibition has been related with a mild decrease in blood pressure of approximately 3-5mmHg in systolic and 1-2mmHg in diastolic blood pressure. These data have been confirmed with 24h ambulatory measurements, as well. Furthermore, given the loss of calories in the urine, a mild decrease in body weight is anticipated, as well. Studies with this class of drugs noted a reduction in body weight of 2 to 3 kg, similar to the loss noted with the use of glucagon-like peptide 1 analogues, the only class of drugs that has offered significant reductions in body weight so far. Consclusion: The beneficial effects of the SGLT-2 inhibition on an abundance of cardiovascular risk factors, including blood pressure and body weight, have created great expectations for potential benefits from the cardiovascular events standpoint, a theory that was confirmed in the two available cardiovascular studies of this promising class of drugs. © 2018 Bentham Science Publishers