How low do we fall to lower hemoglobin A1c? SGLT2 inhibitors: Effective drugs or expensive toxins!

SGLT2 inhibitors improve hyperglycemia with a decline in body weight and blood pressure, the outcomes touted to be of major importance in management of type 2 diabetes. However, the efficacy in lowering glycemia is very modest and imparts an undue cost burden on patients. Moreover, the declines in body weight and blood pressure are slight at best and orthostatic hypotension and its manifestations including syncope at worst, are all secondary to dehydration and probable total body electrolyte depletion caused by polyuria and nocturia as anticipated and established consequences of glycolsuria induced by SGLT2 inhibitors via their mechanism of action. Moreover, frequent adverse effects including impaired renal function as expressed by rises in serum creatinine and urea nitrogen, hyperkalemia and recurrent genitourinary infections are certainly likely to lead to the decline in quality of life. Finally, a rise in LDL cholesterol accompanied by increased serum viscosity secondary to dehydration may compromise cardiovascular safety as well. Thus, use of these expensive agents with modest efficacy and with established significant pathologic side effects escalating costs even further and unknown long term safety may be contradictory to the tenets of ethical medical practice established by “Hippocratic oath”. Recent approval of SGLT2 inhibitors by regulatory agencies in Europe and USA for treatment of hyperglycemia in type 2 diabetes is therefore surprising and disheartening.