Background
Methods
Study design and participants
Outcomes
Statistical analysis
Results
Patient demographics and characteristics
Characteristics | Dapagliflozin (N = 2990) |
---|---|
Age, yearsa | |
No. (missing) | 2990 (0) |
Mean (SD) | 52.6 (12.0) |
Male | |
No. (missing) | 2990 (0) |
No. (%) | 1966 (65.8) |
HbA1cb | |
No. (missing) | 1286 (1722) |
%, mean (SD) | 9.07 (2.0) |
FPG, mmol/L | |
No. (missing) | 1314 (1676) |
Mean (SD) | 10.22 (4.0) |
Body weight, Kg | |
No. (missing) | 408 (2582) |
Mean (SD) | 76.90 (13.9) |
Height, cm | |
No. (missing) | 2879 (111) |
Mean (SD) | 167.42 (8.2) |
BMI, Kg/m2 | |
No. (missing) | 403 (2587) |
Mean (SD) | 27.27 (4.0) |
Median (range) | 26.80 (16.9–45.2) |
BMI category, n (%)c | |
≤18.5 | 2 (0.5) |
>18.5 and <24 | 64 (15.9) |
≥24 and <28 | 189 (46.9) |
≥28 | 148 (36.7) |
Waist circumference, cm | |
No. (missing) | 255 (2635) |
Mean (SD) | 96.21 (10.5) |
SBP, mmHg | |
No. (missing) | 407 (2583) |
Mean (SD) | 131.6 (15.6) |
DBP, mmHg | |
No. (missing) | 407 (2583) |
Mean (SD) | 81.0 (10.1) |
Total cholesterol, mmol/L | |
No. (missing) | 1299 (1691) |
Mean (SD) | 4.87 (1.6) |
HDL-C, mmol/L | |
No. (missing) | 1297 (1693) |
Mean (SD) | 1.15 (0.4) |
LDL-C, mmol/L | |
No. (missing) | 1299 (1691) |
Mean (SD) | 2.79 (1.05) |
Triglycerides, mmol/L | |
No. (missing) | 1301 (1689) |
Mean (SD) | 2.83 (3.2) |
eGFR, ml/min/1.73 m2 | |
No. (missing) | 1298 (1692) |
Mean (SD) | 126.3 (41.1) |
<45 | 3 (0.2) |
≥45 and <60 | 25 (1.9) |
≥60 and <90 | 183 (14.1) |
≥90 | 1087 (83.7) |
Duration of T2DM, yearsd | |
No. (missing) | 2932 (58) |
Mean (SD) | 8.35 (7.1) |
Presence of cardiac disorders, n (%) | |
ASCVD | 640 (21.4) |
Heart failure | 37 (1.2) |
Concomitant antidiabetic medications, n (%) | |
None | 152 (5.1) |
Monotherapy | 2838 (94.9) |
Dual therapy | 2240 (74.9) |
Triple therapy | 1168 (39.1) |
Presence of diabetic complications | |
No. (missing) | 2990 (0) |
No. (%) | 1764 (59.0) |
Real-world use of dapagliflozin and concomitant medications
AEs
Adverse events | Dapagliflozin (N = 2990) |
---|---|
Overall summary, No. (%) | |
≥1 AE | 1059 (35.4) |
≥1 ADRa | 268 (9.0) |
≥1 SAE | 186 (6.2) |
AE leading to discontinuation | 141 (4.7) |
AE of special interest, No. (%) | |
UTI | 70 (2.3) |
GTI | 39 (1.3) |
Hypoglycaemia | 32 (1.1) |
Volume depletion | 9 (0.3) |
Abnormal blood electrolytes | 0 |
Polyuria | 21 (0.7) |
Renal impairment | 8 (0.3) |
Diabetic ketoacidosis | 2 (0.1) |
Hepatic impairment | 7 (0.2) |
Haematuria | 6 (0.2) |
AEs occurring in >0.5% of patients, No. (%) | Mild | Moderate | Severe | Related to study drug | Total |
---|---|---|---|---|---|
Infections and infestations | 228 (7.6) | 40 (1.3) | 9 (0.3) | 2 (0.1) | 277 (9.3) |
Upper respiratory tract infection | 100 (3.3) | 8 (0.3) | 1 (0.0) | 0 | 109 (3.6) |
Bronchitis | 30 (1.0) | 4 (0.1) | 0 | 0 | 34 (1.1) |
Conjunctivitis | 24 (0.8) | 5 (0.2) | 0 | 0 | 29 (1.0) |
Gastrointestinal disorders | 204 (6.8) | 34 (1.1) | 9 (0.3) | 41 (1.4) | 247 (8.3) |
Constipation | 36 (1.2) | 5 (0.2) | 2 (0.1) | 8 (0.3) | 43 (1.4) |
Diarrhoea | 26 (0.9) | 6 (0.2) | 0 | 4 (0.1) | 32 (1.1) |
Metabolism disorders | 183 (6.1) | 22 (0.7) | 11 (0.4) | 56 (1.9) | 216 (7.2) |
Hyperlipidaemia | 34 (1.1) | 1 (0.0) | 0 | 2 (0.1) | 35 (1.2) |
Hyperuricaemia | 31 (1.0) | 2 (0.1) | 0 | 0 | 33 (1.1) |
Hypoglycaemia | 31 (1.0) | 0 | 0 | 19 (0.6) | 31 (1.0) |
Renal and urinary disorders | 126 (4.2) | 15 (0.5) | 2 (0.1) | 74 (2.5) | 143 (4.8) |
Urinary tract infection | 56 (1.9) | 7 (0.2) | 0 | 49 (1.6) | 63 (2.1) |
Musculoskeletal and connective tissue disorders | 117 (3.9) | 22 (0.7) | 1 (0.0) | 8 (0.3) | 140 (4.7) |
Nervous system disorders | 115 (3.8) | 18 (0.6) | 4 (0.1) | 7 (0.2) | 137 (4.6) |
Dizziness | 35 (1.2) | 1 (0.0) | 0 | 2 (0.1) | 36 (1.2) |
Reproductive system and breast disorders | 85 (2.8) | 12 (0.4) | 1 (0.0) | 45 (1.5) | 98 (3.3) |
Investigations | 75 (2.5) | 7 (0.2) | 1 (0.0) | 35 (1.2) | 83 (2.8) |
General administration site conditions disorders | 70 (2.3) | 10 (0.3) | 2 (0.1) | 21 (0.7) | 82 (2.7) |
Skin and subcutaneous tissue disorders | 70 (2.3) | 9 (0.3) | 0 | 10 (0.3) | 79 (2.6) |
Eye disorders | 56 (1.9) | 9 (0.3) | 4 (0.1) | 1 (0.0) | 69 (2.3) |
Cardiac disorders | 42 (1.4) | 13 (0.5) | 5 (0.2) | 3 (0.1) | 60 (2.0) |
Occurring in ≥0.2% of patients, No. (%) | Dapagliflozin (N = 2990) |
---|---|
≥ 1 SAE | 186 (6.2) |
Metabolism and nutrition disorders | 34 (1.1) |
Inadequate control of T2DMa | 20 (0.7) |
Diabetic ketosis | 8 (0.3) |
Hyperglycaemia | 5 (0.2) |
Infections and infestations | 26 (0.9) |
Pneumonia | 8 (0.3) |
Nervous system disorders | 23 (0.8) |
Cerebral infarction | 6 (0.2) |
Cardiac disorders | 21 (0.7) |
Coronary artery disease | 7 (0.2) |
Gastrointestinal disorders | 15 (0.5) |
Large intestine polyp | 5 (0.2) |
Eye disorders | 14 (0.5) |
Musculoskeletal and connective tissue disorders | 12 (0.4) |
Intervertebral disc protrusion | 5 (0.2) |
Injury, poisoning and procedural complications | 9 (0.3) |
Neoplasms | 8 (0.3) |
Renal and urinary disorders | 7 (0.2) |
Vascular disorders | 7 (0.2) |
Hypertension | 5 (0.2) |
General disorders and administration site conditions | 6 (0.2) |
Hepatobiliary disorders | 5 (0.2) |
Reproductive system and breast disorders | 5 (0.2) |
≥1 ADR | 268 (9.0) |
Renal and urinary disorders | 74 (2.5) |
Urinary tract infection | 49 (1.6) |
Metabolism and nutrition disorders | 56 (1.9) |
Hypoglycaemia | 19 (0.6) |
Diabetic ketosis | 15 (0.5) |
Reproductive system and breast disorders | 45 (1.5) |
Vulvovaginal pruritus | 13 (0.4) |
Vaginal infection | 10 (0.3) |
Gastrointestinal disorders | 41 (1.4) |
Dry mouth | 11 (0.4) |
Investigations | 35 (1.2) |
Weight decreased | 17 (0.6) |
General disorders and administration site conditions | 21 (0.7) |
Asthenia | 9 (0.3) |
Thirst | 5 (0.2) |
Skin and subcutaneous tissue disorders | 10 (0.3) |
Musculoskeletal and connective tissue disorders | 8 (0.3) |
Nervous system disorders | 7 (0.2) |
Vascular disorders | 5 (0.2) |
AE leading to discontinuation | |
Renal and urinary disorders | 29 (1.0) |
Urinary tract infection | 14 (0.5) |
Gastrointestinal disorders | 25 (0.8) |
Dry mouth | 5 (0.2) |
Reproductive system and breast disorders | 25 (0.8) |
Vaginal infection | 7 (0.2) |
Vulvovaginal pruritus | 6 (0.2) |
Metabolism and nutrition disorders | 19 (0.6) |
Diabetic ketosis | 7 (0.2) |
Inadequate control of T2DM | 6 (0.2) |
Investigations | 16 (0.5) |
Weight decreased | 9 (0.3) |
General disorders and administration site conditions | 10 (0.3) |
Asthenia | 5 (0.2) |
Skin and subcutaneous tissue disorders | 10 (0.3) |
Pruritis | 5 (0.2) |
Musculoskeletal and connective tissue disorders | 7 (0.2) |
AESIs
Univariate analysis | Multivariate analysisa | ||||
---|---|---|---|---|---|
No. | HR (95% CI) | p value | HR (95% CI) | p value | |
Hypoglycaemia | |||||
Age (>65 years vs 18–65 years) | 2985 | 0.682 (0.206–2.260) | 0.531 | 0.526 (0.107–2.573) | 0.428 |
Sex (female vs male)b | 2986 | 0.913 (0.413–2.017) | 0.821 | 1.254 (0.445–3.533) | 0.669 |
BMI (vs ≥18.5 and <24) | 2852 | ||||
≥24 and <28 | 0.920 (0.350–2.421) | 0.866 | 0.591 (0.162–2.149) | 0.424 | |
≥28 | 0.715 (0.248–2.064 | 0.536 | 0.847 (0.230–3.129) | 0.804 | |
Diabetes duration (per increase of 1 year) | 2928 | 1.064 (1.020–1.109) | 0.004 | – | – |
Diabetes duration (vs ≤ 5 years) | |||||
>5 and ≤10 years | 9.317 (2.065–42.035) | 0.004 | 3.530 (0.670–18.593) | 0.137 | |
>10 and ≤20 years | 4.893 (1.039–23.054) | 0.045 | 2.418 (0.437–13.376) | 0.312 | |
>20 years | 14.995 (3.108–72.349) | <0.001 | 5.932 (0.962–36.557) | 0.055 | |
Presence of T2DM complications (yes vs no)c,d | 2986 | 1.451 (0.656–3.208) | 0.358 | 1.212 (0.369–3.981) | 0.751 |
eGFR (1 ml/min/1.73 m2) (vs ≥90) | 1763 | ||||
≥60 and <90 | 1.743 (0.568–5.350) | 0.331 | 1.697 (0.528–5.455) | 0.375 | |
<60 | 0.000 (0.000–NE) | 0.991 | 0.000 (0.000–NE) | 0.990 | |
Concomitant anti-diabetes medications (vs ≤1) | 2986 | ||||
2 | 1.426 (0.429–4.735) | 0.562 | 3.038 (0.337–27.406) | 0.322 | |
≥3 | 2.647 (0.885–7.919) | 0.082 | 2.318 (0.219–24.577) | 0.485 | |
Insulin use (yes vs no)c | 2986 | 1.882 (0.890–3.979 | 0.098 | 1.760 (0.594–5.218) | 0.308 |
Sulfonylurea use (yes vs no) | 2986 | 1.841 (0.850–3.989) | 0.122 | 1.303 (0.365–4.658) | 0.684 |
Metformin use (yes vs no) | 2986 | 1.792 (0.681–4.714) | 0.237 | 1.292 (0.320–5.222) | 0.719 |
Presence of ASCVD (yes vs no) | 2986 | 0.967 (0.391–2.388) | 0.942 | 1.821 (0.637–5.206) | 0.263 |
Urinary tract infection | |||||
Age (>65 years vs 18–65 years) | 2986 | 1.023 (0.522–2.004) | 0.947 | 1.007 (0.322–3.151) | 0.991 |
Sex (female vs male)b | 2987 | 2.274 (1.406–3.678) | <0.001 | 2.244 (1.047–4.810) | 0.038 |
BMI (vs ≥18.5 and <24) | 2853 | ||||
≥24 and <28 | 1.782 (0.823–3.860) | 0.143 | 1.483 (0.483–4.551) | 0.491 | |
≥28 | 1.642 (0.737–3.658) | 0.225 | 1.468 (0.455–4.741) | 0.521 | |
Diabetes duration (per increase of 1 year) | 2929 | 1.015 (0.983–1.048) | 0.367 | – | – |
Diabetes duration (vs ≤5 years) | |||||
>5 and ≤10 years | 1.053 (0.552–2.007) | 0.876 | 1.556 (0.580–4.178) | 0.380 | |
>10 and ≤20 years | 0.985 (0.543–1.785) | 0.959 | 1.303 (0.487–3.485) | 0.598 | |
>20 years | 1.240 (0.533–2.882) | 0.618 | 0.818 (0.159–4.210) | 0.810 | |
Presence of T2DM complications (yes vs no)c,d | 2987 | 1.073 (0.656–1.755) | 0.780 | 1.025 (0.439–2.392) | 0.954 |
HbA1c % (per increase of 1%) | 1609 | 1.035 (0.882–1.214) | 0.675 | 1.010 (0.781–1.306) | 0.940 |
FPG (per increase of 1 mmol/L) | 1823 | 1.023 (0.945–1.108) | 0.568 | 1.054 (0.923–1.204) | 0.438 |
eGFR (1 ml/min/1.73 m2) (vs ≥90) | 1763 | ||||
≥60 and <90 | 1.479 (0.680–3.219) | 0.324 | 1.387 (0.507–3.796) | 0.524 | |
< 60 | 0.000 (0.000–NE) | 0.986 | 0.000 (0.000–NE) | 0.989 | |
Genital tract infection | |||||
Age (> 65 years vs 18–65 years) | 2984 | 0.780 (0.275–2.215) | 0.641 | 0.757 (0.153–3.738) | 0.733 |
Sex (female vs male)b | 2985 | 4.006 (1.951–8.229) | <0.001 | 6.723 (2.135–21.167) | 0.001 |
BMI (vs ≥18.5 and <24) | 2851 | ||||
≥24 and <28 | 1.475 (0.405–5.371) | 0.556 | 2.543 (0.344–18.790) | 0.360 | |
≥28 | 3.678 (1.091–12.395) | 0.036 | 6.701 (0.948–47.380) | 0.057 | |
Diabetes duration (per increase of 1 year) | 2927 | 1.039 (0.996–1.084) | 0.076 | – | – |
Diabetes duration (vs ≤5 years) | |||||
>5 and ≤10 years | 1.698 (0.674–4.278) | 0.262 | 6.107 (1.212–30.785) | 0.028 | |
>10 and ≤20 years | 1.158 (0.457–2.935) | 0.756 | 4.184 (0.743–23.560) | 0.105 | |
>20 years | 2.824 (1.003–7.954) | 0.049 | 20.580 (3.448–122.828) | < 0.001 | |
Presence of T2DM complications (yes vs no)c,d | 2985 | 0.321 (0.156–0.659) | 0.002 | 0.153 (0.048–0.481) | 0.001 |
HbA1c % (per increase of 1%) | 1609 | 0.878 (0.692–1.115) | 0.286 | 1.101 (0.771–1.572) | 0.597 |
FPG (per increase of 1 mmol/L) | 1823 | 0.971 (0.863–1.093) | 0.626 | 0.897 (0.724–1.112) | 0.322 |
eGFR (1 ml/min/1.73 m2) (vs ≥90) | 1764 | ||||
≥60 and <90 | 0.203 (0.026–1.621) | 0.133 | 0.298 (0.037–2.432) | 0.258 | |
<60 | 0.000 (0.000–NE) | 0.990 | 0.000 (0.000–NE) | 0.992 |