Table 1.

Subgroup analyses from major SGLT2 inhibitor trials with respect to adverse event profiles of SGLT2 inhibitors in participants with different baseline eGFRs [25–28]

Trial (SGLT2 inhibitor studied)	Adverse event profile of SGLT2 inhibitors in participants with different baseline eGFRs
EMPA-REG OUTCOME (empagliflozin)	Similar in participants with eGFR < 45, 45 to < 60, and ≥ 60 mL/min/1.73 m2
CANVAS Program (canagliflozin)	Consistent across eGFR subgroups (< 45, 45 to < 60, 60 to < 90, and ≥ 90 mL/min/1.73 m2); however, trend (P heterogeneity = 0.06) for higher risk of hypoglycaemia in lower eGFR subgroup—noted that subgroups with lower eGFR had higher insulin use
DECLARE-TIMI 58 (dapagliflozin)	Consistent across eGFR subgroups (< 60, 60 to < 90, and ≥ 90 mL/min/1.73 m2)
CREDENCE (canagliflozin)	Consistent across eGFR subgroups (30 to < 45, 45 to < 60, and 60 to < 90 mL/min/1.73 m2 at screening) with respect to serious adverse events, amputation, and fracture. However, significant interaction test for volume depletion (P = 0.01), hazard ratio of volume depletion for participants with eGFR 30 to < 45 mL/min/1.73 m2 1.99 (95% CI 1.33–2.98) (canagliflozin vs placebo), compared with hazard ratio for participants with eGFR 60 to < 90 mL/min/1.73 m2 0.89 (0.58–1.38)

CI confidence interval, eGFR estimated glomerular filtration rate, SGLT2 sodium-glucose cotransporter 2