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Table 2 Adverse events in the Dapagliflozin Effect on CardiovascuLAR Events (DECLARE-TIMI 58), CANagliflozin CardioVascular Assessment Study (CANVAS) Program, Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients–Removing Excess Glucose (EMPA–REG OUTCOME), and Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trials

From: Class effects of SGLT2 inhibitors on cardiorenal outcomes

  DECLARE-TIMI 58 CANVAS EMPA–REG OUTCOME CREDENCE
DAPA n (%) Placebo n (%) Riska HR (95% CI) p-value CANA event rate Placebo event rate Riska p-value Pooled EMPA n (%) Placebo n (%) Riska p-value CANA n (%) Placebo n (%) CANA event rate Placebo event rate Riska HR (95% CI)
Male genital infectionb 76 (0.9) 9 (0.1) +c 8.36 (4.19–16.68)c 0.001c 34.9 10.8 +c < 0.001c 166 (5.0) 25 (1.5) +c < 0.001c 28 (0.2) 3 (0.0) 8.4 0.9 +c 9.30 (2.83–30.60)c
Female genital infectionb 68.8 17.5 +c < 0.001c 135 (10.0) 17 (2.6) +c < 0.001c 22 (0.3) 10 (0.0) 12.6 6.1 + 2.10 (1.00–4.45)
Any AE N/A N/A N/A N/A N/A N/A N/A N/A N/A 4230 (90.2) 2139 (91.7) c < 0.001c 1784 (8.1) 1860 (0.8) 351.4 379.3 c 0.87 (0.82–0.93)c
Serious AE 2925 (34.1) 3100 (36.2) c 0.91 (0.87–0.96)c < 0.001c 104.3 120 c 0.04c 1789 (38.2) 988 (42.3) c < 0.001c 737 (3.3) 806 (0.4) 145.2 164.4 c 0.87 (0.79–0.97)c
AE leading to discontinuation 693 (8.1) 592 (6.9) +c 1.15 (1.03–1.28)c 0.01c 35.5 32.8 + 0.07 813 (17.3) 453 (19.4) c < 0.001c N/A N/A N/A N/A N/A N/A
Hypoglycemia 58 (0.7) 83 (1.0) c 0.68 (0.49–0.95)c 0.02c 50 46.4 + 0.20 1303 (27.8) 650 (27.9) N/A 225 (1.0) 240 (0.1) 44.3 48.9 0.92 (0.77–1.11)
UTI 127 (1.5) 133 (1.6) 0.93 (0.73–1.18) 0.54 40 37 + 0.38 842 (18.0) 423 (18.1) N/A 245 (1.1) 221 (0.1) 48.3 45.1 + 1.08 (0.90–1.29)
Fracture 457 (5.3) 440 (5.1) + 1.04 (0.91–1.18) 0.59 15.4 11.9 +c 0.02c 179 (3.8) 91 (3.9) N/A 67 (0.3) 68 (0.0) 11.8 12.1 0.98 (0.70–1.37)
Hyperkalemia N/A N/A N/A N/A N/A 6.9 4.4 + 0.10 N/A N/A N/A N/A 151 181 29.7 36.9 0.80
Amputation 123 (1.4) 113 (1.3) + 1.09 (0.84–1.40) 0.53 6.3 3.4 +c < 0.001c N/A N/A N/A N/A 70 (0.3) 63 (0.0) 12.3 11.2 + 1.11 (0.79–1.56)
AKI 125 (1.5) 113 (1.3) c 0.69 (0.55–0.87)c 0.002c 3 4.1 0.33 45 (1.0) 37 (1.6) c < 0.05c 86 (0.4) 98 (0.0) 16.9 20 0.85 (0.64–1.13)
Breast cancer 36 (0.4) 113 (1.3) 0 1.02 (0.64–1.63) 0.92 3.1 2.6 + 0.65 N/A N/A N/A N/A 8 (0.1) 3 (0.0) 4.1 1.6 + 2.59 (0.69–9.76)
Bladder cancer 26 (0.3) 45 (0.5) c 0.57 (0.35–0.93)c 0.02c 1 1.1 0.74 N/A N/A N/A N/A 10 (0.0) 9 (0.0) 1.7 1.6 + 1.10 (0.45–2.72)
DKA 27 (0.3) 12 (0.1) +c 2.18 (1.10–4.30)c 0.02c 0.6 0.3 + 0.14 4 (0.1) 1 (<  0.1) + N/A 11 (0.0) 1 (0.0) 2.2 0.2 +c 10.80 (1.39–83.65)c
  1. DAPA dapagliflozin, CANA canagliflozin, EMPA empagliflozin, HR hazard ratio, CI confidence interval, AE adverse event, N/A not available, UTI urinary tract infection, AKI acute kidney injury, DKA diabetic ketoacidosis
  2. aIndicates increased (“+”), decreased (“−”), or no difference in (“0”) risk associated with study drug compared to placebo.
  3. bDECLARE-TIMI 58 did not differentiate genital infection by sex
  4. cItalic indicates statistical significance at the α = 0.05 level