Genital infections seem to be the most common adverse effect of gliflozins. In clinical trials mycotic infections, urinary tract infections and osmotic diuresis were higher in patients treated with gliflozins. In May 2015, the FDA issued a warning that gliflozins can increase risk of diabetic ketoacidosis (DKA). By reducing glucose blood circulation, gliflozins cause less stimulation of endogenous insulin secretion or lower dose of exogenous insulin that results in diabetic ketoacidosis. They can specifically cause euglycemic DKA (euDKA, DKA where the blood sugar is not elevated) because of the renal tubular absorption of ketone bodies. A particularly high risk period for ketoacidosis is the perioperative period.<unk> s may need to be discontinued before surgery, and only recommended when someone is not unwell, is adequately hydrated and able to consume a regular diet. In September 2015, the FDA issued a warning related to canagliflozin (Invokana) and canagliflozin/metformin (Invokamet) due to decreased bone mineral density and therefore increased risk of bone fractures. Using gliflozins in combination therapy with metformin can lower the risk of hypoglycemia compared to other T2DM such as sulfonylureas and insulin. Increased risk of lower limb amputation is associated with canagliflozin but further data is needed to confirm this risk associated with different gliflozins. A European Medicines Agency review concluded that there is a potential increased risk of lower limb amputation (mostly affecting the toes) in people taking canagliflozin, dapagliflozin and empagliflozin. In August 2018, the FDA issued a warning of an increased risk of Fournier gangrene in patients using<unk> s. The absolute risk is considered very low. To lessen the risk of developing ketoacidosis (a serious condition in which the body produces high levels of blood acids called ketones) after surgery, the FDA has approved changes to the prescribing information for<unk>  diabetes medicines to recommend they be stopped temporarily before scheduled surgery. Canagliflozin, dapagliflozin, and empagliflozin should each be stopped at least three days before, and ertugliflozin should be stopped at least four days before scheduled surgery. Symptoms of ketoacidosis include nausea, vomiting, abdominal pain, tiredness, and trouble breathing.
SGLT2 inhibitor
Chloride channel opener
COX-2 inhibitor
CYP17A1 inhibitor
Norepinephrine–dopamine disinhibitor
Beta-adrenergic agonist
Reuptake inhibitor
Protein kinase inhibitor