What is a unique risk associated with SGLT2 inhibitors?

• A. Euglycemic diabetic ketoacidosis
• B. Severe hypoglycemia always
• C. Lactic acidosis
• D. Pancreatitis

Answer: (A)

SGLT2 inhibitors carry a distinctive risk of euglycemic diabetic ketoacidosis, where a diabetic ketoacidosis picture develops even when blood glucose is only mildly elevated or near normal. This happens because blocking glucose reabsorption in the kidneys causes glucosuria and lower plasma glucose, which can mask the typical high glucose seen in DKA. At the same time, relative insulin deficiency or inadequate insulin action, coupled with increased glucagon, promotes lipolysis and ketone production. The result is metabolic acidosis driven by ketones with glucose levels that aren’t as high as in classic DKA, which is why it’s easy to overlook.

This risk is what sets euDKA apart from other possibilities. Severe hypoglycemia is not a characteristic feature of these drugs and occurs only in specific contexts when other glucose-lowering therapies are involved. Lactic acidosis is more commonly linked to metformin, not SGLT2 inhibitors. Pancreatitis isn’t a recognized unique association with SGLT2 inhibitors.