The Cardiovascular and Blood Pressure Effects and Safety of the SGLT2 Inhibitors

Type 2 diabetes mellitus is an independent risk factor for Cardiovascular Disease (CVD) and hypertension and patients with Type2 DM has a two-to four fold risk in developing CVD than nondiabetic persons [1]. For very long time, management of Type2 DM was focused on controlling blood glucose, since hyperglycemia has been associated with increased cardiovascular risk [2,3], but aggressive blood glucose control has not produced the expected beneficial cardiovascular effects, but rather an in increase in cardiovascular complications, possibly due to metabolic or hyperglycemic memory of blood vessels [2,4-6]. However, the treatment of chronic hyperglycemia with the use of traditional antihyperglycemic drugs has not clearly shown a reduction of cardiovascular events [1]. The discovery and marketing of new drugs that lower blood glucose independently of insulin action have shown promising results in reducing Cardiovascular Disease (CVD) and Blood Pressure (BP) by recent studies [7,8]. This new class of drugs exerts their effects through inhibition of Sodium-Glucose Cotransporter2 (SGLT2) in the proximal renal tubule and interferes with glucose reabsorption [9]. The renal glucose loss leads to decease in blood glucose and energy loss leading to reduction in body weight. However, besides their promising antidiabetic and cardiovascular and BP effects, there are some warning signs of serious adverse effects investigated by the Food and Drug Administration (FDA). There are 3 SGLT2 inhibitors approved and marketed in the US, canaglifloxin, dapaglifloxin, and empaglifloxin (table 1), and their beneficial cardiovascular and blood pressure effects together with their adverse effects, will be discussed in this commentary.