Table 3

SGLT2 inhibitors: safety issues

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.