APPENDIX 4Detailed Outcome Data
Table 12Other Efficacy Outcomes
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| Metformin +SU |
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| Empagliflozin 10
N = 217 | Empagliflozin 25
N = 214 | Placebo
N = 206 |
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| Health Care Resource Utilization |
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| Any hospitalization since last HCRU reporting, week 24, n (%) | 2 (1) | 0 | 4 (2) |
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| diabetes-related | 0 | 0 | 0 |
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| Any ED visit since last HCRU reporting, week 24, n (%) | 1 (1) | 4 (2) | 1 (1) |
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| diabetes-related | 0 | 0 | 0 |
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| Any unscheduled outpatient visit since last HCRU reporting, week 24, n (%) | 27 (13) | 19 (10) | 28 (14) |
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| diabetes-related | 3 | 5 | 7 |
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| Any HC provider home visit since last HCRU reporting, week 24, n (%) | 0 | 1 (1) | 0 |
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| diabetes-related | 0 | 0 | 0 |
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| Any days when patient was unable to perform his/her paid work due to diabetes since last scheduled HCRU reporting, week 24, n (%) | 0 | 0 | 0 |
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| EQ–5D: mobility, n (%) | Baseline | Week24 | Baseline | Week24 | Baseline | Week24 |
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| No problems | 206 (92) | 174 (94) | 195 (91) | 163 (90) | 202 (91) | 158 (93) |
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| Some problems | 19 (8) | 12 (7) | 19 (9) | 19 (10) | 21 (9) | 12 (7) |
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| Confined to bed | 0 | 0 | 0 | 0 | 0 | 0 |
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| EQ–5D: self–care, n (%) | | | | | | |
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| No problems | 218 (97) | 181 (98) | 207 (97) | 176 (97) | 219 (98) | 165 (97) |
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| Some problems | 7 (3) | 4 (2) | 7 (3) | 5 (3) | 4 (2) | 5 (3) |
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| Unable to wash or dress | 0 | 0 | 0 | 0 | 0 | 0 |
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| EQ–5D: usual activities, n (%) | | | | | | |
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| No problems | 212 (94) | 170 (91) | 197 (92) | 168 (93) | 201 (91) | 161 (95) |
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| Some problems | 12 (5) | 15 (8) | 17 (8) | 13 (7) | 20 (9) | 8 (5) |
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| Unable to perform | 1 (1) | 1 (1) | 0 | 0 | 1 (1) | 1 (1) |
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| EQ–5D: pain/discomfort, n (%) | | | | | | |
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| No pain | 162 (72) | 140 (75) | 158 (74) | 134 (74) | 157 (70) | 129 (76) |
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| Moderate pain | 59 (26) | 45 (24) | 55 (26) | 47 (26) | 64 (29) | 40 (24) |
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| Extreme pain | 3 (1) | 1 (1) | 1 (1) | 1 (1) | 2 (1) | 1 (1) |
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| EQ–5D: anxiety/depression, n (%) | | | | | | |
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| Not anxious | 195 (87) | 163 (88) | 186 (87) | 159 (88) | 181 (81) | 145 (85) |
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| Moderately anxious | 29 (13) | 23 (12) | 28 (13) | 20 (11) | 39 (18) | 23 (14) |
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| Extremely anxious | 1 (<1) | 0 | 0 | 2 (1) | 3 (1) | 2 (1) |
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| EQ–5D: state of health (VAS) | Baseline | Change at week 24 | Baseline | Change at week 24 | Baseline | Change at week 24 |
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| Mean (SD) | 81.0 (11.6) | 3.6 (11.5) | 80.9 (13.3) | 2.3 (11.7) | 78.8 (13.8) | 2.2 (10.9) |
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| | N = 186 | | N = 180 | | N = 169 |
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EQ-5D = EuroQol 5-Dimension Health-Related Quality of Life questionnaire; ED = emergency department; HC = health care; HCRU = health care resource utilization; SD = standard deviation; SU = sulfonylurea; VAS = visual analogue scale.
Source: Clinical study report for study 23.1
Table 13Subgroup Analyses for Primary Outcome
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| Study 23 (Metformin +SU) |
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| A1C: Mean Change From Baseline | Empagliflozin 10 N = 225 | Empagliflozin 25 N = 216 | Placebo N = 225 |
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| Based on Baseline A1C: | | | |
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| A1C < 8.5% | | | |
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| Mean (SD) baseline | 7.64 (0.50) | 7.66 (0.47) | 7.66 (0.45) |
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| N | 157 | 151 | 151 |
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| Mean (SD) change from baseline | −0.56 (0.60) | −0.60 (0.69) | −0.11 (0.74) |
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| Adjusteda mean (SE) | −0.56 (0.06) | −0.60 (0.06) | −0.12 (0.06) |
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| Adjusteda mean (95% CI) difference from placebo | 10 mg: −0.44 (−0.61 to −0.28), P < 0.0001
25 mg: −0.48 (−0.65 to −0.32), P < 0.0001 |
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| A1C ≥ 8.5% | | | |
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| Mean (SD) baseline | 9.05 (0.48) | 9.11 (0.56) | 9.14 (0.45) |
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| N | 68 | 65 | 74 |
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| Mean (SD) change from baseline | −1.36 (0.86) | −1.17 (0.87) | −0.33 (0.92) |
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| Adjusteda mean (SE) | −1.35 (0.09) | −1.14 (0.09) | −0.33 (0.08) |
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| Adjusteda mean (95% CI) difference from placebo | 10 mg: −1.02 (−1.26 to −0.78), P < 0.0001
25 mg: −0.81 (−1.05 to −0.56), P < 0.0001 |
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| | | |
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| Interaction by A1C value | P = 0.0005 | | |
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| Based on Baseline eGFR (MDRD) [mL/min/1.73m2]: |
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| ≥ 90 mL/min/1.73 m2 (normal) | | | |
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| Mean (SD) baseline | 8.05 (0.82) | 8.11 (0.86) | 8.22 (0.84) |
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| N | N = 92 | N = 94 | N = 94 |
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| Mean (SD) change from baseline | −0.90 (0.72) | −0.95 (0.82) | −0.24 (0.82) |
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| Adjusteda mean (SE) | −0.90 (0.07) | −0.92 (0.07) | −0.17 (0.07) |
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| Adjusteda mean (95% CI) difference from placebo | 10 mg: −0.73 (−0.94 to −0.53), P < 0.0001
25 mg: −0.75 (−0.96 to −0.55), P < 0.0001 |
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| 60 to < 90 mL/min/1.73 m2 (mild impairment) | | | |
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| Mean (SD) baseline | 8.08 (0.84) | 8.14 (0.83) | 8.11 (0.85) |
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| N | N = 114 | N = 105 | N = 109 |
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| Mean (SD) change from baseline | −0.79 (0.76) | −0.68 (0.74) | −0.22 (0.76) |
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| Adjusteda mean (SE) | −0.81 (0.07) | −0.68 (0.07) | −0.23 (0.07) |
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| Adjusteda mean (95% CI) difference from placebo | 10 mg: −0.58 (−0.76 to −0.39), P < 0.0001
25 mg: −0.45 (−0.64 to −0.26), P < 0.0001 |
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| 30 to < 60 mL/min/1.73 m2 (moderate impairment) | | | |
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| Mean (SD) baseline | 8.03 (0.63) | 7.74 (0.60) | 8.03 (0.63) |
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| N | N = 19 | N = 17 | N = 22 |
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| Mean (SD) change from baseline | −0.40 (1.01) | −0.31 (0.66) | 0.25 (0.90) |
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| Adjusteda mean (SE) | −0.44 (0.16) | −0.48 (0.17) | 0.15 (0.15) |
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| Adjusteda mean (95% CI) difference from placebo | 10 mg: −0.58 (−1.02 to −0.14), P = 0.0093
25 mg: −0.63 (−1.08 to −0.18), P = 0.0063 |
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| Interaction by baseline eGFR | P = 0.3111 | | |
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A1C = glycated hemoglobin; ANCOVA = analysis of covariance; CI = confidence interval; eG FR = estimated glomerular filtration rate; MDRD = Modification of Diet in Renal Disease; SD = standard deviation; SE = standard error.
- a
The ANCOVA model included treatment, renal function, region, treatment by baseline A1C interaction, and baseline A1C. ANCOVA models were fitted for each subgroup separately by modelling the primary end point with treatment, baseline A1C, renal function, geographical region, subgroup, and treatment-by-subgroup interaction terms, with exceptions and details specified in the statistical analysis plan. Very small subgroups, with fewer than 21 patients in total, were excluded from the ANCOVA analyses but were included in the descriptive statistics. Statistically significant treatment-by-subgroup interactions were defined as those with P values less than 0.1.
Source: Clinical study report for study 23.1
