SGLT-2 inhibitors: the glucosuric antidiabetics

Abstract

Despite availability of a number of oral antidiabetics, a sizeable population of diabetics remains uncontrolled. Thus there is growing need of new group of drugs for diabetic control. Understanding renal conservation of glucose by efficient reabsorption through sodium glucose cotransporter-2 (SGLT-2) has paved way for development of an entirely new group of drugs, the SGLT-2 inhibitors. These glucosuric antidiabetic agents have shown promise in early clinical studies. Canagliflozin is recently approved for use in diabetes alone or along with other antidiabetics. Other highly selective inhibitors undergoing various stages of clinical developments are dapagliflozin, sergliflozin, remogliflozin, ipragliflozin, empagliflozin, luseogliflozin, tofogliflozin and desoxyrhaponticin. KGA-2727 (pyrazole-O-glucoside) is the first selective SGLT-1 inhibitor undergoing intense preclinical testing. There are safety issues associated with this group like urogenital infections (fungal), weight loss, initial osmotic diuresis and increased incidence of cardiovascular events. The long term safety remains to be established. Despite these limitations, SGLT-2 inhibition offers a unique target for achieving adequate control of diabetes in adults. [Int J Basic Clin Pharmacol 2013; 2(4.000): 347-352

Sodium glucose co-transporter 2 inhibitors for glycemic control in type 2 diabetes mellitus: Quality of reporting of randomized controlled trials

“…Sodium glucose co-transporter 2 (SGLT2) inhibitors provide a novel therapeutic strategy to augment renal glucose excretion in type 2 diabetic patients. [ 4 ] A number of compounds belonging to this group have been discovered. Of these, canagliflozin, dapagliflozin and empagliflozin are approved by US Food and Drug Administration for use as monotherapy or adjunct to other oral antidiabetic drugs for the management of type 2 DM.…”

“…Among other SGLT2 inhibitors undergoing various stages of development are remogliflozin, ipragliflozin, sergliflozin, luseogliflozin, tofogliflozin and desoxyrhaponticin. [ 4 ] The efficacy and safety of these agents for controlling hyperglycemia in type 2 diabetes has been evaluated in several clinical trials and meta-analyses with some concerns like urogenital infections, cardiovascular events, bladder and breast cancers. [ 4 5 6 ]…”

Development and Recent Advancement of SGLT2 Inhibitors for the Treatment Regime of T2DM

“…Structurally, it is a benzylphenol based O-glucoside SGLT2 inhibitor glucoside. Interestingly, during study, sergliflozin was found to act as a prodrug and its active form sergliflozin-A behaved as a potent SGLT2 inhibitor (52). Further study also reported that sergliflozin-A was approximately several times more active against SGLT2 compared to phlorizin.…”

Oral Hypoglycaemic Agents: Non-Insulin Medications for Type 2 Diabetes Patients

“…These lower HbA1c up to 0.6-0.9% by inhibiting the absorption of glucose from the proximal tubule of the kidney, causing glycosuria, and also lower both body weight and blood pressure, and may benefit those who are overweight or obese. On the other hand, these do not cause hypoglycaemia (Thaddanee et al, 2013). Some SGLT-2 agents are Canagliflozin, Dapagliflozin, Sergliflozin, Remogliflozin, Ipragliflozin, Empagliflozin, Luseogliflozin, Tofogliflozin, and Desoxyrhaponticin.…”