| Unadjusted | PS-IPW model | |||||
|---|---|---|---|---|---|---|
| (by stabilized ATE with trimming) | ||||||
| Males, | Females, | p-value* | Males, | Females, | Standardized difference | |
| n = 361 | n = 282 | n = 342† | n = 270† | |||
| Age (years) | 55.7 ± 12.5 | 56.6 ± 13.8 | 0.39 | 56.8 ± 13.4 | 56.7 ± 14.0 | 0.01 |
| Type of preceding drug (SGLT2i-preceding) (%)) | 182 (50%) | 130 (46%) | 0.28 | 164 (48%) | 126 (47%) | 0.03 |
| History of T2D > 10 years (%) | 291 (81%) | 227 (81%) | 0.73 | 274 (80%) | 217 (80%) | 0.01 |
| BW (kg) | 85.0 ± 19.4 | 72.3 ± 16.2 | < 0.001 | 83.8 ± 19.1 | 71.4 ± 14.8 | 0.84 |
| BMI | 29.5 ± 5.9 | 29.8 ± 6.1 | 0.50 | 29.4 ± 5.9 | 29.3 ± 5.5 | 0.02 |
| SBP (mmHg) | 133.1 ± 19.3 | 134.4 ± 17.8 | 0.37 | 133.9 ± 21.4 | 133.4 ± 17.2 | 0.03 |
| DBP (mmHg) | 79.1 ± 13.2 | 75.6 ± 12.4 | < 0.001 | 77.7 ± 13.5 | 76.8 ± 12.4 | 0.07 |
| MAP (mmHg) | 97.1 ± 13.8 | 95.2 ± 12.3 | 0.07 | 96.4 ± 14.1 | 95.7 ± 12.4 | 0.06 |
| HbA1c (mmol/mol [%]) | 71.4 ± 18.0 (8.7 ± 1.6) | 73.4 ± 18.0 (8.9 ± 1.6) | 0.17 | 71.6 ± 19.6 (8.7 ± 1.8) | 72.0 ± 16.7 (8.7 ± 1.5) | 0.02 |
| eGFR (mL/min/1.73 m2) | 76.8 ± 27.6 | 80.7 ± 27.1 | 0.08 | 77.8 ± 29.0 | 78.9 ± 25.9 | 0.04 |
| LnACR | 3.87 ± 2.00 | 3.61 ± 1.82 | 0.09 | 3.74 ± 1.95 | 3.72 ± 1.79 | 0.01 |
| AST (IU/mL) | 29.7 ± 19.2 | 29.9 ± 20.9 | 0.91 | 29.2 ± 20.4 | 29.3 ± 20.1 | 0.01 |
| ALT(IU/mL) | 40.5 ± 30.3 | 34.0 ± 28.0 | 0.01 | 36.3 ± 26.7 | 36.0 ± 32.0 | 0.01 |
| FIB-4 index | 1.25 ± 0.70 | 1.33 ± 0.92 | 0.19 | 1.32 ± 0.87 | 1.29 ± 0.76 | 0.04 |
| Duration of the preceding treatment (month) | 27.6 ± 28.4 | 28.4 ± 20.2 | 0.59 | 28.2 ± 21.3 | 29.9 ± 21.8 | 0.08 |
| Duration of the combination treatment (month) | 33.5 ± 16.8 | 34.2 ± 17.5 | 0.59 | 33.9 ± 16.6 | 33.5 ± 18.3 | 0.02 |
| Total duration of the study (month) | 61.1 ± 22.7 | 62.7 ± 25.6 | 0.40 | 62.1 ± 24.2 | 63.4 ± 28.3 | 0.05 |
| Type of SGLT2i | ||||||
| Ipragliflozin | 33 (9%) | 34 (12%) | 0.15 | 35 (10%) | 27 (10%) | 0.01 |
| Dapagliflozin | 82 (23%) | 76 (27%) | 0.15 | 81 (24%) | 62 (23%) | 0.02 |
| Tofogliflozin | 38 (11%) | 31 (11%) | 37 (11%) | 26 (10%) | 0.04 | |
| Luseogliflozin | 14 (4%) | 18 (7%) | 19 (6%) | 12 (4%) | 0.05 | |
| Canagliflozin | 41 (11%) | 26 (9%) | 40 (12%) | 31 (11%) | 0.01 | |
| Empagliflozin | 95 (26%) | 52 (18%) | 78 (23%) | 71 (26%) | 0.08 | |
| SGLT2i was changed during the treatment periods | 58 (16%) | 45 (16%) | 52 (15%) | 41 (15%) | 0.001 | |
| Type of | ||||||
| GLP1-Ra | ||||||
| Liraglutide | 133 (37%) | 81 (29%) | 0.29 | 115 (34%) | 88 (33%) | 0.02 |
| Dulaglutide | 134 (37%) | 112 (40%) | 0.29 | 131 (38%) | 103 (38%) | 0.01 |
| Exenatide | 4 (1%) | 4 (1%) | 5 (1%) | 4 (1%) | 0.002 | |
| Lixisenatide | 6 (2%) | 3 (1%) | 5 (1%) | 6 (3%) | 0.06 | |
| GLP1-Ra was changed during the treatment periods | 84 (23%) | 82 (29%) | 86 (25%) | 69 (26%) | 0.01 | |
| Concomitant medications | ||||||
| Sulphonylureaa | 119 (33%) | 80 (28%) | 0.21 | 109 (32%) | 91 (34%) | 0.04 |
| Metformin | 196 (54%) | 163 (58%) | 0.37 | 186 (54%) | 143 (53%) | 0.03 |
| Insulin | 150 (42%) | 131 (47%) | 0.21 | 147 (43%) | 112 (41%) | 0.03 |
| Pioglitazone | 61 (17%) | 25 (9%) | 0.003 | 40 (12%) | 26 (10%) | 0.07 |
| αGI | 55 (15%) | 33 (12%) | 0.20 | 43 (13%) | 38 14%) | 0.04 |
| Glinide | 16 (4%) | 12 (4%) | 0.91 | 13 (4%) | 11 (4%) | 0.01 |
| RAS inhibitor | 192 (43%) | 134 (48%) | 0.15 | 172 (50%) | 135 (50%) | 0.01 |
| CCB | 138 (38%) | 100 (36%) | 0.47 | 125 (37%) | 91 (34%) | 0.06 |
| β blocker | 73 (20%) | 29 (10%) | < 0.001 | 55 (16%) | 45 (17%) | 0.02 |
| MRB | 13 (4%) | 13 (5%) | 0.52 | 16 (5%) | 10 (4%) | 0.05 |
| Thiazide | 28 (8%) | 17 (6%) | 0.39 | 22 (6%) | 15 (6%) | 0.04 |
| Loop | 22 (6%) | 16 (6%) | 0.82 | 20 (6%) | 16 (6%) | 0.01 |
| Statin | 184 (51%) | 136 (48%) | 0.49 | 168 (46%) | 133 (49%) | 0.01 |
| PS-IPW model by stabilized ATE with trimming | |||
|---|---|---|---|
| Males, | Females, | GLM# | |
| n = 342＊ | n = 270＊ | ||
| Renal outcomes and function | |||
| a) Incidence of renal composite outcome | 96 (28%) | 70 (26%) | 0.90 [0.56-1.44], p = 0.65 |
| Progression of ACR status | 34 (19%) | 44 (16%) | 0.85 [0.50-1.45], p = 0.55 |
| ≥30% decrease in the eGFR | 40 (12%) | 30 (11%) | 0.95 [0.49-1.86], p = 0.89 |
| b) Changes in eGFR | |||
| Annual changes in the eGFR (mL/min/1.73 m2/year) | −1.7 ± 3.9 | −1.8 ± 3.9 | −0.1 [−0.8 to 0.7], p = 0.89 |
| c) Changes in LnACR | 0.13 ± 1.55 | −0.08 ± 1.62 | −0.21 [0.06-0.31], p = 0.17 |
| Clinical characteristics after combination treatment | |||
| eGFR (mL/min/1.73 m2) | 69.2 ± 26.9 | 71.6 ± 26.9 | 2.3 [−2.6 to 7.3], p = 0.35 |
| LnACR | 3.86 ± 1.90 | 3.64 ± 1.75 | −0.23 [−0.55 to 0.09], p = 0.16 |
| BW (kg) | 79.6 ± 17.4 | 66.6 ± 14.7 | −13.0 [−15.8 to −10.3], p < 0.001 |
| BMI | 27.9 ± 5.4 | 27.3 ± 5.5 | −0.6 [−1.5 to 0.3], p = 0.21 |
| SBP (mmHg) | 129.2 ± 16.47 | 127.4 ± 16.1 | −1.7 [−4.6 to 1.2], p = 0.25 |
| DBP (mmHg) | 75.7 ± 3.9 | 72.4 ± 11.8 | −3.3 [−5.8 to −0.9], p = 0.01 |
| MAP (mmHg) | 93.5 ± 3.45 | 90.7 ± 11.5 | −2.8 [−5.1 to −0.5], p = 0.02 |
| HbA1c (mmol/mol [%]) | 63.1 ± 16.1 (7.9 ± 1.5) | 63.8 ± 15.9 (8.0 ± 1.5) | 0.7 [−2.3 to 3.6] (0.1 [−0.2 to 0.3]), p = 0.67 |
| AST (IU/L) | 26.2 ± 5.0 | 24.8 ± 17.4 | −1.4 [−4.4 to 1.7], p = 0.38 |
| ALT (IU/L) | 31.0 ± 22.5 | 27.1 ± 18.3 | −3.9 [−7.4 to −0.4], p = 0.03 |
| FIB-4 index | 1.37 ± 0.75 | 1.41 ± 0.94 | 0.05 [−0.11 to 0.20], p = 0.56 |
| Change in the clinical findings | |||
| Change in BW (kg) | −4.2 ± 7.3 | −4.8 ± 7.3 | −0.6 [−1.8 to 0.6], p = 0.33 |
| Change in BMI | −1.5 ± 2.5 | −2.0 ± 2.9 | −0.5 [−1.0 to −0.1], p = 0.03 |
| Change in SBP (mmHg) | −4.7 ± 23.4 | −5.9 ± 18.6 | −1.2 [−5.0 to 2.6], p = 0.53 |
| Change in DBP (mmHg) | −2.0 ± 13.8 | −4.5 ± 12.9 | −2.5 [−4.9 to −0.1], p = 0.04 |
| Change in MAP (mmHg) | −2.9 ± 15.1 | −5.0 ± 13.1 | −2.1 [−4.6 to 0.4], p = 0.10 |
| Change in HbA1c (mmol/mol [%]) | −8.5 ± 20.8 (−0.8 ± 1.9) | −8.2 ± 20.3 (−0.7 ± 1.9) | 0.3 [−3.5 to 4.1] (0.0 [−0.3 to 0.4]), p = 0.89 |
| Change in AST (IU/L) | −3.0 ± 19.8 | −4.5 ± 19.5 | −1.5 [−5.1 to 2.1], p = 0.42 |
| Change in ALT (IU/L) | −5.3 ± 24.0 | −8.9 ± 29.2 | −3.6 [−8.9 to 1.7], p = 0.18 |
| Change in FIB-4 index | 0.05 ± 0.63 | 0.12 ± 0.74 | 0.07 [−0.06 to 0.21], p = 0.29 |
