Table 3.

Mitigation strategies for adverse events associated with the use of SGLT2is

Adverse risks	Mitigation strategies
Genital infections	•Prior to prescribing SGLT2is, patients should be informed about the risk of genital infections •Patient counseling to maintain good genital hygiene •Patients' education about the signs and symptoms of genital infections •If a patient develops an uncomplicated fungal infection, discontinuation of SGLT2is is not required; rather management with antifungal medications •For those with a history of recurring genital infections, prophylactic antifungal treatment is recommended (to be reviewed after 6 months or earlier if needed)
UTI	•Discontinue SGLT2is when treating pyelonephritis or urosepsis •Caution should be taken when prescribing SGLT2is to a patient with recurrent UTI
DKA	•Prior to initiating SGLT2is, assessment of predisposing factors for DKA •Discontinue SGLT2is, if a patient develops DKA •Patient education about signs/symptoms to help early detection of DKA •Follow-up with blood or urine ketones in high-risk individuals •Sick-day protocol •Restriction on the ketogenic diet, alcohol abuse •Maintaining a minimum low dose of insulin if needed •Consider temporarily stopping SGLT2is, if one chooses intermittent fasting (e.g. for Ramadan) •Undertaking ketone testing for diabetic patients, if unwell •Exercise caution when starting SGLT2is in patients with T1DM and T2DM (consult diabetologist, if needed) •Discontinue SGLT2is for 3 days before surgery or during acute illness
Volume depletion	•Discontinuation of SGLT2is is not required •Regular monitoring of volume status and kidney function •Dose adjustment of diuretics in high-risk patients •Temporarily withhold SGLT2is during acute illness
AKI	•Careful interpretation of initial decline in eGFR after initiating SGLT2is, considering expected drug effect to avoid unwarranted discontinuation of treatment
Amputations	•Routine preventive foot care measures for those at high risk of amputation •Avoid initiating SGLT2is in the presence of active foot infection or ulceration •Discontinue SGLT2is, if foot complications occur during treatment •Consider re-initiating SGLT2i therapy after complete resolution of foot complications
Fractures	•For patients with CKD treated with SGLT2is, monitoring of bone parameters (calcium, phosphate, and PTH) as appropriate for the CKD stage

AKI, acute kidney injury; CKD, chronic kidney disease; DKA, diabetic ketoacidosis; eGFR, estimated glomerular filtration rate; PTH, parathyroid hormone; SGLT2i, sodium-glucose cotransporter-2 inhibitor; T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; UTI, urinary tract infection.