What is an SGLT2 Inhibitor?

SGLT2 Inhibitors are prescription medications that are supposed to help lower blood sugar in adults with type 2 diabetes. SGLT2 is short for sodium-glucose co-transporter-2.

These medications are approved by the Food & Drug Administration to lower blood sugar by causing the kidneys to remove sugar from the body through the urine. The currently available SGLT2 Inhibitors are:

What is the deficiency of these drugs?

The U.S. Food and Drug Administration (FDA) is warning that the type 2 diabetes medicine canagliflozin, Dapagliflozin, and Empagliflozin may lead to ketoacidosis, a serious condition where the body produces high levels of blood acids called ketones that may require hospitalization.

SGLT2 inhibitors trigger multiple mechanisms that could predispose to diabetic ketoacidosis. When SGLT2 inhibitors are combined with insulin, it is often necessary to decrease the insulin dose to avoid hypoglycemia. The lower dose of insulin may be insufficient to suppress lipolysis and ketogenesis. Furthermore, SGLT2 is expressed in pancreatic α-cells, and SGLT2 inhibitors promote glucagon secretion.

Based on the physiology of SGLT2 and the pharmacology of SGLT2 inhibitors, there are several biologically plausible mechanisms whereby this class of drugs has the potential to increase the risk of developing diabetic ketoacidosis.

What is Diabetic Ketoacidosis?

Diabetic Ketoacidosis can be life threatening.  The condition occurs when the body’s cells are unable to get the sugar they need for energy.  Starved of those vital sugars, the body then begins to break down fat and muscle for energy instead and releases ketones into the blood.

The release of Ketones into the blood results in too much acid in the blood: a chemical imbalance known as ketoacidosis.  Diabetic Ketoacidosis may require hospitalization for treatment and can result in diabetic coma, brain swelling, or even death.

FDA Strengthens AKI Warning for Some SGLT2 Inhibitors

Since the approval of canagliflozin in March 2013 up until October 2015, the FDA received reports of 101 confirmable cases of acute kidney injury (canagliflozin=73, dapagliflozin=28) with canagliflozin or dapagliflozin use. Hospitalization was required for 96 cases, in which 22 involved admission to the intensive care unit; 4 deaths occurred during hospitalization. Also, 15 patients received dialysis, of which 3 had a history of chronic kidney disease or previous acute kidney injury; 6 patients reported concomitant use of ACE inhibitor and a diuretic. For approximately half of the cases, acute kidney injury occurred within 1 month of starting the drug; most patients improved upon discontinuing the drug.