Table 3.
Association of sodium–glucose cotransporter 2 inhibitors and glucose‐lowering medications with fracture
| Class | Drug | n | ROR | PRR | IC | EBGM |
|---|---|---|---|---|---|---|
| (95% two‐sided CI) | (χ2) | (IC025) | (EBGM05) | |||
| SGLT2is | Canagliflozin | 162 | 0.49 (0.42–0.57) | 0.49 (86.54) | −1.02 (−) | 0.49 (0.43) |
| Dapagliflozin | 78 | 0.54 (0.43–0.67) | 0.54 (30.66) | −0.88 (−) | 0.54 (0.45) | |
| Empagliflozin | 75 | 0.42 (0.33–0.52) | 0.42 (60.56) | −1.25 (−) | 0.42 (0.35) | |
| Ertugliflozin | 2 | 0.31 (0.08–1.26) | 0.32 (3.00) | −1.66 (−) | 0.32 (0.10) | |
| Ipragliflozin | 0 | – | – | – | – | |
| Luseogliflozin | 0 | – | – | – | – | |
| Remogliflozin | 0 | – | – | – | – | |
| Tofogliflozin | 0 | – | – | – | – | |
| GLMs | Metformin | 767 | 0.38 (0.36–0.41) | 0.39 (753.68) | −1.36 (−) | 0.39 (0.37) |
| Glyburide | 7 | 0.48 (0.23–1.01) | 0.48 (3.92) | −1.05 (−) | 0.48 (0.26) | |
| Glipizide | 9 | 0.26 (0.14–0.51) | 0.27 (18.30) | −1.90 (−) | 0.27 (0.15) | |
| Glimepiride | 14 | 0.52 (0.31–0.88) | 0.53 (6.06) | −0.93 (−) | 0.53 (0.34) | |
| Exenatide | 407 | 0.42 (0.38–0.46) | 0.42 (321.92) | −1.23 (−) | 0.43 (0.39) | |
| Lixisenatide | 5 | 2.24 (0.92–5.46) | 2.2 (3.32)† | 1.14 (0.47)† | 2.20 (1.04) | |
| Liraglutide | 60 | 0.15 (0.12–0.19) | 0.15 (287.36) | −2.71 (−) | 0.15 (0.12) | |
| Albiglutide | 12 | 0.10 (0.05–0.17) | 0.1 (102.95) | −3.37 (−) | 0.10 (0.06) | |
| Dulaglutide | 88 | 0.25 (0.20–0.31) | 0.25 (200.15) | −1.99 (−) | 0.25 (0.21) | |
| Pioglitazone | 267 | 1.24 (1.10–1.40)† | 1.24 (12.20) | 0.31 (0.27)† | 1.24 (1.12) | |
| Rosiglitazone | 606 | 0.46 (0.42–0.50) | 0.46 (384.27) | −1.11 (−) | 0.46 (0.43) | |
| Sitagliptin | 202 | 0.47 (0.41–0.54) | 0.48 (117.88) | −1.07 (−) | 0.48 (0.42) | |
| Saxagliptin | 21 | 0.43 (0.28–0.66) | 0.44 (15.56) | −1.20 (−) | 0.44 (0.30) | |
| Alogliptin | 11 | 1.18 (0.65–2.14) | 1.18 (0.30) | 0.24 (0.13)† | 1.18 (0.71) | |
|
GLMs+ SGLT2is |
Metformin + SGLT2is | 105 | 0.47 (0.39–0.57) | 0.47 (63.07) | −1.08 (−) | 0.47 (0.40) |
| Glyburide + SGLT2is | 2 | 0.38 (0.10–1.54) | 0.39 (1.96) | −1.37 (−) | 0.39 (0.12) | |
| Glipizide + SGLT2is | 10 | 0.71 (0.38–1.33) | 0.71 (1.16) | −0.48 (−) | 0.71 (0.42) | |
| Glimepiride + SGLT2is | 7 | 0.42 (0.20–0.88) | 0.42 (5.59) | −1.24 (−) | 0.42 (0.23) | |
| Exenatide + SGLT2is | 12 | 0.55 (0.31–0.96) | 0.55 (4.47) | −0.86 (−) | 0.55 (0.34) | |
| Lixisenatide + SGLT2is | 0 | – | – | – | – | |
| Liraglutide + SGLT2is | 10 | 0.44 (0.24–0.83) | 0.45 (6.93) | −1.16 (−) | 0.45 (0.27) | |
| Albiglutide + SGLT2is | 0 | – | – | – | – | |
| Dulaglutide + SGLT2is | 11 | 0.39 (0.22–0.71) | 0.39 (10.35) | −1.34 (−) | 0.39 (0.24) | |
| Pioglitazone + SGLT2is | 10 | 0.73 (0.39–1.37) | 0.74 (0.97) | −0.44 (−) | 0.74 (0.44) | |
| Rosiglitazone + SGLT2is | 0 | – | – | − | – | |
| Sitagliptin + SGLT2is | 22 | 0.45 (0.29–0.68) | 0.45 (15.07) | −1.15 (−) | 0.45 (0.32) | |
| Saxagliptin + SGLT2is | 10 | 0.95 (0.51–1.78) | 0.95 (0.02) | −0.07 (−) | 0.95 (0.57) | |
| Alogliptin + SGLT2is | 1 | 0.80 (0.11–5.78) | 0.81 (0.05) | −0.31 (−) | 0.81 (0.15) |
CI, confidence interval; EBGM, empirical Bayes geometric mean; EBGM05, the lower 90% one‐sided confidence interval of empirical Bayes geometric mean; GLMs, glucose‐lowering medications; IC, information component; IC025, the lower limit of the 95% two‐sided confidence interval of the information component; n, the reported number of drug‐associated fractures; PRR, proportional reporting ratio; ROR, reporting odds ratio; SGLT2is, sodium‐glucose cotransporter 2 inhibitors.
†
Positive signal.