- A systematic review/meta-analysis has shown no consistent evidence of sodium-glucose cotransporter 2 inhibitors (SGLT2is) exposure and increased amputation risk.
Why this matters
- Meta-analysis included 12 randomized controlled trials (RCTs) of 45,551 participants (n=25,593 receiving SGLT2i, n=600 alternative treatment, n=19,358 placebo).
- Funding: Monument Analytics.
- Random effect meta-analysis of 7 RCTs suggested no statistically significant association between SGLT2i exposure and amputation risk, with evidence of substantial statistical heterogeneity (risk ratio, 1.28; 95% CI, 0.93-1.76; I2=62.0%; P=.12).
- Fixed-effects analysis showed an increased risk, however, again with statistical heterogeneity (1.27; 95% CI, 1.09-1.48; I2=62%; P=.003).
- In a subgroup analysis of canagliflozin vs placebo, a statistically significantly increased risk emerged in a fixed-effects meta-analysis (relative risk, 1.59; 95% CI, 1.26-2.01; I2=88%; P=.0001), but no effect with dapagliflozin or empagliflozin.
- In observational data, study heterogeneity and potential confounding prevented meta-analysis, although two-thirds of comparisons with other drug classes showed a nonsignificant increased amputation risk.
- Limited statistical power to detect rare events.
- Amputation was not a prespecified outcome in any trial.
- No individual patient-level data.
- Considerable heterogeneity across studies.