Table 3.

SGLT2 inhibitors: safety issues

	Canagliflozin	Dapagliflozin	Empagliflozin	Ertugliflozin
Urinary tract infections (low dose)*	2.1 (100 mg)	2.0 (5 mg)	1.7 (10 mg)	0.1 (5 mg)
Urinary tract infections (high dose)*	0.6 (300 mg)	0.6 (10 mg)	0 (25 mg)	0.2 (15 mg)
Genital infections (female) (low dose)*	7.8 (100 mg)	6.9 (5 mg)	3.9 (10 mg)	6.1 (5 mg)
Genital infections (female) (high dose)*	8.8 (300 mg)	5.4 (10 mg)	4.9 (25 mg)	9.2 (15 mg)
Genital infections (male) (low dose)*	3.5 (100 mg)	2.5 (5 mg)	2.7 (10 mg)	3.3 (5 mg)
Genital infections (male) (high dose)*	3.1 (300 mg)	2.4 (10 mg)	1.2 (25 mg)	3.8 (15 mg)
Δ LDL cholesterol (mg/dL) (low dose)	+4.5 (100 mg)		+2.3 (10 mg)	+2.6 (5 mg)
Δ LDL cholesterol (mg/dL) (high dose)	+8.0 (300 mg)	+3.9 (10 mg)	+4.2 (25 mg)	+5.4 (15 mg)
Amputations (placebo)	1.5 (placebo)			0.1 (placebo)
Amputations (low dose)	3.5 (100 mg)			0.2 (5 mg)
Amputations (high dose)	3.1 (300 mg)			0.5 (15 mg)
Bone fractures (canagliflozin)	4.0 (CANVAS)
Bone fractures (placebo)	2.6 (CANVAS)

Data are %, unless otherwise indicated. Selected data on various adverse effects are summarized for the four FDA-approved SGLT2 inhibitors and have been taken from the FDA-approved prescribing information for each drug. In some cases, the prescribing information provides data separately for placebo- and drug-treated patients. In those cases, we have calculated placebo-subtracted data by subtracting the data on placebo-treated patients from data on drug-treated patients. Puckrin et al. (84) conducted a meta-analysis of 86 randomized clinical trials. They reported a 3.37-fold (95% CI 2.89–3.93) increase in the risk of genital infections relative to placebo and a 3.89-fold (95% CI 3.14–4.82) increase relative to active comparators. They did not observe an increased risk of urinary tract infections: risk relative to placebo 1.03 (95% CI 0.96–1.11) and risk relative to active comparator 1.08 (0.93–1.25).

*Calculated by subtracting incidence in placebo-treated patients from incidence in drug-treated patients.