Table 1.

Practical considerations with use of SGLT2is [17, 18, 51, 53]

Potential adverse events	Practical considerations
Any patient initiating SGLT2is
Volume depletion	Increased risk with concomitant use of SGLT2i and diuretic; a diuretic dose adjustment may need to be considered
	Educate patients about the potential for orthostatic hypotension and the importance of monitoring body weight and blood pressure on a regular basis, particularly in the first week of SGLT2i therapy
	Provide preemptive guidance to patients to contact a HCP if they lose ≥ 1.4 kg over a 24-h period, ≥ 1.8 kg in a week, or in a setting of symptomatic hypotension
Genital and UTIs	Mycotic infections are more common among female and uncircumcised male individuals
	HCP should reinforce the importance of adequate hygiene
	Advise patients to immediately contact a HCP to report any genital/perineal tenderness, redness, or swelling
	There is no significant increase in the risk of UTIs
Renal injury	Baseline and periodic monitoring of renal function is recommended when starting SGLT2i therapy [17]
	Modest initial decrease in eGFR (3–4 mL/min/1.73 m2) expected with SGLT2i initiation
	In patients with impaired renal function, monitoring renal function is recommended during the first few weeks of SGLT2i therapy [17, 18, 51, 53]
	Cases of acute kidney injury are rare, except in concert with volume depletion [18]
Adverse drug–drug interaction	Pharmacokinetic drug–drug interactions are minimal
	Co-administration of canagliflozin, a P-glycoprotein substrate, with digoxin may increase digoxin plasma levels. It is important to monitor digoxin levels and any signs or symptoms of toxicity with concomitant use of canagliflozin and digoxin
Specific considerations in patients with T2D
Hypoglycemia	This is uncommon; however, there is an increased risk with concomitant use of sulfonylureas or insulin
	Dose adjustments or discontinuation of the sulfonylurea or reduction of the total daily insulin dose by < 20% could reduce the risk of hypoglycemia [51]
DKA	Advise patients about DKA risk, identifying the following symptoms of DKA: fruity breath odor, thirst, polyuria, nausea/vomiting, abdominal pain, confusion, and fever
	For high-risk patients, home monitoring with urine ketone test strips may be advised
	Precautions to take to lower DKA risk:
	Avoid preemptive, substantial reductions (> 20%) in daily insulin dose [51]
	Use caution with low carbohydrate diets, which may result in excessive ketosis
	Limit excessive alcohol intake
	Discontinue SGLT2i ≥ 3 days before surgery to prevent postoperative ketoacidosis [17]
	Asymptomatic elevations in β-hydroxybutyrate are frequent with SGLT2is, but only a fraction of cases lead to overt DKA
Lower limb amputations	Predominantly toe and metatarsal
	More apparent with the SGLT2i canagliflozin
	Increased risk with previous amputations or with established peripheral artery disease
	Educate patients, especially those with diabetic neuropathy, about performing regular foot exams and seeing a podiatrist annually

DKA diabetic ketoacidosis, eGFR estimated glomerular filtration rate, HCP healthcare provider, SGLT2i sodium–glucose cotransporter 2 inhibitor, T2D type 2 diabetes, UTIs urinary tract infections