Table 1. Characteristics of included studies.
| Study | Dose | Control group | Duration of follow-up (weeks) | Sample size | Mean age (years) | Mean duration of diabetes (years) | Mean baseline HbA1C (%) | Mean baseline blood pressure (mmHg) | Mean baseline eGFR (ml/min/ 1.73 m2) | Mean baseline urine ACR (mg/g) | Reported outcomes of CKD patients | Outcomes reported |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CANAGLIFLOZIN | ||||||||||||
| Bode et al. (2013) | 100 mg, 300 mg | Placebo | 26 | 584 | 63.6 | 11.7 | 7.7 | 131.0/75.7 | 77.5 | N.R. | No | eGFR |
| Cefalu et al. (2013) | 100 mg, 300 mg | Glimepiride | 52 | 1,038 | 56.2 | 6.6 | 7.8 | 129.8/79.0 | N.R. | 29.1 | No | eGFR, uACR |
| Lavalle-Gonzalez et al. (2013) | 100 mg, 300 mg | Sitagliptin | 52 | 873 | 55.5 | 6.9 | 7.9 | 128.2/77.7 | 89.7 | N.R. | No | eGFR |
| Schernthaner et al. (2013) | 300 mg | Sitagliptin | 52 | 460 | 56.7 | 9.6 | 8.1 | 130.7/78.9 | 88.9 | N.R. | No | eGFR |
| Wilding et al. (2013a) IJCP | 100 mg, 300 mg | Placebo | 52 | 306 | 56.8 | 9.6 | 8.1 | 130.4/78.7 | 90.3 | N.R. | No | eGFR |
| Yale et al. (2013) | 100 mg, 300 mg | Placebo | 26 | 211 | 68.5 | 16.3 | 8.0 | 134.9/74.4 | 39.4 | 30.0 (median) | Yes | eGFR, uACR |
| Forst et al. (2014) | 100 mg, 300 mg | Placebo (26 weeks) + sitagliptin (26 weeks) | 52 | 261 | 57.4 | 10.5 | 7.9 | 127.1/76.4 | 86.4 | N.R. | No | eGFR |
| Inagaki et al. (2014) | 100 mg, 200 mg | Placebo | 24 | 240 | 58.0 | 5.4 | 8.0 | 127.9/77.8 | 84.4 | N.R. | No | uACR |
| Qiu, Capuano & Meininger (2014) | 50 mg bid, 150 mg bid | Placebo | 18 | 239 | 57.4 | 7.0 | 7.6 | 129.3/78.1 | 85.9 | N.R. | No | eGFR |
| Sha et al. (2014) | 300 mg | Placebo | 12 | 35 | 62.8 | 8.5 | 7.7 | 132.9/80.0 | 97.3 | N.R. | No | eGFR |
| Ji et al. (2015) | 100 mg, 300 mg | Placebo | 18 | 636 | 56.2 | 6.7 | 8.0 | 129.5/77.3 | 94.0 | N.R. | No | eGFR |
| Rodbard et al. (2016) | 100 mg or 300 mg (titrated)a | Placebo | 26 | 171 | 57.4 | 9.9 | 8.5 | N.R. | 90.5 | N.R. | No | eGFR |
| Rosenstock et al. (2016) | 100 mg, 300 mg | Placebo | 26 | 618 | 54.9 | 3.2 | 8.8 | 128.6/78.3 | 87.0 | N.R. | No | eGFR |
| DAPAGLIFLOZIN | ||||||||||||
| Wilding et al. (2009) | 10 mg, 20 mg | Placebo | 12 | 68 | 56.7 | 12.3 | 8.4 | 128.8/77.4 | 87.6 | N.R. | No | eGFR |
| Strojek et al. (2011) | 2.5 mg, 5 mg, 10 mg | Placebo | 24 | 596 | 59.8 | 7.4 | 8.1 | N.R. | 76.7 | N.R. | No | eGFR |
| Nauck et al. (2011) | 2.5 mg–10 mg (titrated)b | Glipizide | 52 | 814 | 58.5 | 6.5 | 7.7 | 133.3/80.6 | 90.1 | 58.0 | No | eGFR, uACR |
| Bolinder et al. (2012) | 10 mg | Placebo | 24 | 167 | 60.7 | 5.8 | 7.2 | 134.6/80.5 | 84.3 | 44.3 | No | eGFR, uACR |
| Wilding et al. (2012) | 2.5 mg, 5 mg, 10 mg | Placebo | 48 | 658 | 59.3 | 13.6 | 8.5 | 138.5/80.1 | 78.4 | 75.2 | No | eGFR, uACR |
| Lambers Heerspink et al. (2013) | 10 mg | Placebo | 12 | 48 | 55.9 | 6.5 | 7.6 | 136.41/82.0 | N.R. | N.R. | No | eGFR |
| Ji et al. (2014) | 5 mg, 10 mg | Placebo | 24 | 338 | 51.4 | 1.4 | 8.3 | 123.6/77.8 | 92.5 | N.R. | No | eGFR |
| Kohan et al. (2014) | 5 mg, 10 mg | Placebo | 104 | 132 | 67.0 | 16.9 | 8.4 | 132.1/73.3 | 44.6 | N.R. | Yes | eGFR, uACR |
| Schumm-Draeger et al. (2015) | 2.5 mg bid, 5 mg bid, 10 mg qd | Placebo | 16 | 400 | 57.7 | 5.2 | 7.8 | 132.0/80.7 | 86.3 | N.R. | No | eGFR |
| Bailey et al. (2015) | 2.5 mg, 5 mg, 10 mg | Placebo 24 weeks + 500 mg metformin | 102 | 274 | 52.2 | 1.9 | 7.9 | 125.9/80.5 | 85.1 | 23.5 | No | eGFR, uACR |
| Weber et al. (2016) | 10 mg | Placebo | 12 | 449 | 56.5 | 7.5 | 8.1 | 151.1/91.3 | 85.9 | 143.7 | No | eGFR, uACR |
| EMPAGLIFLOZIN | ||||||||||||
| Haring et al. (2013) | 10 mg, 25 mg | Placebo | 24 | 666 | 57.1 | N.R. | 8.1 | 128.9/78.6 | 87.2 | N.R. | No | eGFR |
| Roden et al. (2013) | 10 mg, 25 mg | Placebo | 24 | 676 | 54.7 | N.R. | 7.9 | 131.1/78.8 | N.R. | N.R. | No | eGFR |
| Barnett et al. (2014) | 10 mg, 25 mg | Placebo | 52 | 637 | 64.1 | N.R. | 8.0 | 135.3/76.9 (CKD2) | 71.6 (CKD2) | 155.0 (CKD2) | Yes | eGFR, uACR |
| 133.7/76.7 (CKD3) | 44.9 (CKD3) | 362.5 (CKD3) | ||||||||||
| 145.6/77.6 (CKD4) | 23.2 (CKD4) | 1387.4 (CKD4) | ||||||||||
| Haring et al. (2014) | 10 mg, 25 mg | Placebo | 24 | 637 | 55.7 | N.R. | 7.9 | 129.4/78.7 | 89.0 | N.R. | No | eGFR |
| Kovacs et al. (2014) | 10 mg, 25 mg | Placebo | 24 | 498 | 54.5 | N.R. | 8.1 | 126.1/76.9 | 85.7 | N.R. | No | eGFR |
| Rosenstock et al. (2014) | 10 mg, 25 mg | Placebo | 52 | 563 | 56.7 | N.R. | 8.3 | 126.2/78.2 | N.R. | N.R. | No | eGFR |
| Ridderstrale et al. (2014) | 25 mg | Glimepiride | 104 | 1500 | 56.0 | N.R. | 7.9 | 133.5/79.5 | 88.0 | 40.2c | Yes | eGFR, uACR |
| Kadowaki et al. (2014) | 5 mg, 10 mg, 25 mg, 50 mg | Placebo | 12 | 547 | 57.5 | N.R. | 8.0 | 129.2/78.7 | 85.7 | N.R. | No | eGFR |
| DeFronzo et al. (2015) | 10 mg, 25 mg | Linagliptin | 52 | 313 | 55.9 | N.R. | 8.0 | 129.8/79.3 | 90.5 | 52.2 | No | eGFR, uACR |
| Lewin et al. (2015) | 10 mg, 25 mg | Linagliptin | 52 | 340 | 54.6 | N.R. | 8.0 | 128.5/78.8 | 88.8 | 36.8 | No | eGFR, uACR |
| Tikkanen et al. (2015) | 10 mg, 25 mg | Placebo | 12 | 723 | 60.2 | N.R. | 7.9 | 142.1/83.9 | 84.0 | N.R. | No | eGFR |
| Nishimura et al. (2015) | 10 mg, 25 mg | Placebo | 4 | 60 | 62.7 | N.R. | 7.9 | 120.9/72.4 | 80.0 | N.R. | No | eGFR |
| Rosenstock et al. (2015) | 10 mg, 25 mg | Placebo | 78 | 364 | 58.8 | N.R. | 8.2 | 133.0/78.3 | 84.0 | N.R. | No | eGFR |
| Ross et al. (2015) | 12.5 mg bid, 25 mg qd, 5 mg bid, 10 mg qd | Placebo | 16 | 965 | 58.2 | N.R. | 7.8 | 131.3/78.6 | 89.2 | N.R. | No | eGFR |
| Wanner et al. (2016) | 10 mg, 25 mg | Placebo | 156(median) | 3064 | 63.1 | N.R. | 8.07 | 135.5/76.7 | 74.1 | N.R. | Yes | eGFR |
| IPRAGLIFLOZIN | ||||||||||||
| Wilding et al. (2013b) DOM | 12.5 mg, 50 mg, 150 mg, 300 mg | Placebo | 12 | 304 | 57.4 | 5.9 | 7.8 | N.R. | N.R. | N.R. | No | eGFR |
| Fonseca et al. (2013) | 12.5 mg, 50 mg, 150 mg, 300 mg | Placebo | 12 | 304 | 53.7 | 4.6 | 7.9 | N.R. | N.R. | N.R. | No | eGFR |
| Kashiwagi et al. (2015a) DI EMIT | 50 mg | Placebo | 24 | 240 | 59.7 | 10.5 | 8.4 | 130.0/76.6 | 84.7 | 50.8 | No | eGFR, uACR |
| Kashiwagi et al. (2015b) DI BRIGHTEN | 50 mg | Placebo | 16 | 129 | 59.4 | 6.7 | 8.3 | 130.0/128.2 | 87.8 | N.R. | No | eGFR |
| Kashiwagi et al. (2015c) DI SPOTLIGHT | 50 mg | Placebo | 24 | 151 | 56.2 | 6.8 | 9.3 | 130.4/77.9 | 91.0 | 39.3 | No | eGFR, uACR |
| Kashiwagi et al. (2015d) DOM LANTERN | 50 mg | Placebo | 24 | 164 | 64.4 | 9.5 | 7.5 | 133.3/77.3 | 60.9 | 148.2 | Yes | eGFR, uACR |
| Lu et al. (2016) | 50 mg | Placebo | 24 | 170 | 53.7 | 6.2 | 7.7 | N.R. | 149.2 | N.R. | No | eGFR, uACR |
| TOFOGLIFLOZIN | ||||||||||||
| Kaku et al. (2014) | 10 mg, 20 mg, 40 mg | Placebo | 24 | 212 | 57.3 | 6.4 | 8.4 | 129.2/78.3 | 85.4 | N.R. | No | eGFR |
Notes.
a
After six weeks, the canagliflozin dose was increased from 100 to 300 mg (or from placebo to matching placebo) if all of the following criteria were met: baseline eGFR ≥ 70 ml/min/1.73 m2; fasting self-monitored blood glucose ≥ 5.6 mmol/l (100 mg/dl); and no volume depletion-related adverse events within two weeks before dose increase.
b
From week 0 to week 18 (titration period), patients received an initial dose of dapagliflozin of 2.5 mg, which was up-titrated for patients with fasting blood glucose ≥ 110 mg/dl (6.1 mmol/l) until the maximum dose of 10 mg was reached. From week 19 to week 52 (maintenance period), the dose was no longer up-titrated but could be down-titrated in the event of recurrent hypoglycemia.
c
Mean baseline urine ACRs: normoalbuminuric group, 9.55 mg/g; microalbuminuric group, 86.3 mg/g; and macroalbuminuric group, 728.9 mg/g.
Abbreviations
- N.R.
- not reported
- uACR
- urine albumin/creatinine ratio
- IJCP
- International Journal of Clinical Practice
- DOM
- Diabetes, Obesity and Metabolism
- DI
- Diabetology International
EMIT, BRIGHTEN, SPOTLIGHT, and LANTERN are names of randomized controlled trials.