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.