TABLE 1.
Baseline characteristics of the study population (demographics, lifestyle factors, diabetes complications and other comorbidities)
| Pre‐matched | Matched | |||||
|---|---|---|---|---|---|---|
| SGLT2 inhibitor cohort | DPP‐4 inhibitor cohort | SMD | SGLT2 inhibitor cohort | DPP‐4 inhibitor cohort | SMD | |
| Number of patients | 13 617 | 29 426 | 8650 | 8650 | ||
| Age at index, mean (SD) years | 57.71 (10.64) | 65.97 (12.83) | 0.701 | 58.97 (10.65) | 58.97 (11.56) | 0.000 |
| Age group, n (%) | ||||||
| 18‐54 years | 5401 (39.66) | 6151 (20.90) | 3087 (35.69) | 3210 (37.11) | ||
| 55‐64 years | 4675 (34.33) | 7011 (23.83) | 2965 (34.28) | 2748 (31.77) | ||
| 65‐74 years | 2964 (21.77) | 8511 (28.92) | 2103 (24.31) | 1969 (22.76) | ||
| 75+ years | 577 (4.24) | 7753 (26.35) | 495 (5.72) | 723 (8.36) | ||
| Male, n (%) | 7626 (56.00) | 16 438 (55.86) | 0.003 | 4942 (57.13) | 4945 (57.17) | 0.001 |
| Ethnicity, n (%) | 0.092 | 0.028 | ||||
| White | 6650 (48.84) | 14 220 (48.32) | 4208 (48.65) | 4140 (47.86) | ||
| Black | 159 (1.17) | 563 (1.91) | 117 (1.35) | 111 (1.28) | ||
| South Asian | 521 (3.83) | 1481 (5.03) | 374 (4.32) | 370 (4.28) | ||
| Mixed race | 92 (0.68) | 267 (0.91) | 73 (0.84) | 65 (0.75) | ||
| Other ethnic minorities | 42 (0.31) | 111 (0.38) | 31 (0.36) | 41 (0.47) | ||
| Missing | 6153 (45.19) | 12 784 (43.44) | 3847 (44.47) | 3923 (45.35) | ||
| Townsend deprivation quintile, n (%) | 0.082 | 0.009 | ||||
| 1 (least deprived) | 1827 (13.42) | 4484 (15.24) | 1196 (13.83) | 1206 (13.94) | ||
| 2 | 1943 (14.27) | 4539 (15.43) | 1248 (14.43) | 1262 (14.59) | ||
| 3 | 2359 (17.32) | 5300 (18.01) | 1495 (17.28) | 1489 (17.21) | ||
| 4 | 2381 (17.49) | 5066 (17.22) | 1465 (16.94) | 1451 (16.77) | ||
| 5 (Most deprived) | 1973 (14.49) | 3882 (13.19) | 1233 (14.25) | 1246 (14.40) | ||
| Missing | 3134 (23.02) | 6155 (20.92) | 2013 (23.27) | 1996 (23.08) | ||
| Calendar year at index, n (%) | 0.666 | 0.026 | ||||
| 2012 | 0 (0) | 994 (3.38) | 0 (0) | 0 (0) | ||
| 2013 | 491 (3.61) | 5703 (19.38) | 352 (4.07) | 359 (4.15) | ||
| 2014 | 1727 (12.68) | 5166 (17.56) | 975 (11.27) | 997 (11.53) | ||
| 2015 | 2551 (18.73) | 5151 (17.50) | 1494 (17.27) | 1561 (18.05) | ||
| 2016 | 2991 (21.97) | 4552 (15.47) | 1900 (21.97) | 1900 (21.97) | ||
| 2017 | 3043 (22.35) | 4139 (14.07) | 1994 (23.05) | 1939 (22.42) | ||
| 2018 | 2814 (20.67) | 3721 (12.65) | 1935 (22.37) | 1894 (21.90) | ||
| Lifestyle variables, n (%) | ||||||
| Obesity | 10 741 (78.88) | 16 581 (56.35) | 0.496 | 6304 (72.88) | 6329 (73.17) | 0.007 |
| Overweight | 2661 (19.54) | 9670 (32.86) | 0.306 | 2047 (23.66) | 2035 (23.53) | 0.003 |
| Smoking status | 7832 (57.52) | 16 031 (54.48) | 0.061 | 4910 (56.76) | 4918 (56.86) | 0.002 |
| Alcohol abuse | 9038 (66.37) | 18 235 (61.97) | 0.092 | 5735 (66.30) | 5726 (66.20) | 0.002 |
| Drug abuse | 182 (1.34) | 262 (0.89) | 0.043 | 110 (1.27) | 116 (1.34) | 0.006 |
| Diabetes complications, n (%) | ||||||
| Diabetic retinopathy | 7752 (56.93) | 16 057 (54.57) | 0.048 | 4363 (50.44) | 4462 (51.58) | 0.023 |
| Diabetes with other ophthalmic manifestations | 325 (2.39) | 1367 (4.65) | 0.123 | 217 (2.51) | 220 (2.54) | 0.002 |
| Retinal detachment, vitreous haemorrhage, vitrectomy | 106 (0.78) | 306 (1.04) | 0.028 | 61 (0.71) | 58 (0.67) | 0.004 |
| Retinal laser coagulation therapy | 75 (0.55) | 119 (0.40) | 0.021 | 23 (0.27) | 28 (0.32) | 0.011 |
| Diabetic neuropathy | 2535 (18.62) | 5926 (20.14) | 0.039 | 1369 (15.83) | 1404 (16.23) | 0.011 |
| Diabetic nephropathy | 65 (0.48) | 586 (1.99) | 0.137 | 31 (0.36) | 33 (0.38) | 0.004 |
| Hypoglycaemia | 463 (3.40) | 1118 (3.80) | 0.021 | 237 (2.74) | 241 (2.79) | 0.003 |
| Hyperglycaemia | 490 (3.60) | 1010 (3.43) | 0.009 | 243 (2.81) | 238 (2.75) | 0.004 |
| Disorders of fluid electrolyte and acid‐base balance | 5 (0.04) | 56 (0.19) | 0.046 | 4 (0.05) | 2 (0.02) | 0.012 |
| Diabetic ketoacidosis | 30 (0.22) | 44 (0.15) | 0.016 | 10 (0.12) | 17 (0.20) | 0.021 |
| Hyperosmolar hyperglycaemic nonketotic syndrome | 5 (0.04) | 21 (0.07) | 0.015 | 2 (0.02) | 3 (0.03) | 0.007 |
| Diabetes with peripheral circulatory disorders | 5 (0.04) | 64 (0.22) | 0.051 | 4 (0.05) | 5 (0.06) | 0.005 |
| Diabetic foot | 13 203 (96.96) | 28 184 (95.78) | 0.063 | 8298 (95.93) | 8304 (96.00) | 0.004 |
| Gangrene | 6 (0.04) | 38 (0.13) | 0.029 | 5 (0.06) | 2 (0.02) | 0.017 |
| Lower extremity amputation | 77 (0.57) | 233 (0.79) | 0.028 | 50 (0.58) | 47 (0.54) | 0.005 |
| Osteomyelitis | 70 (0.51) | 183 (0.62) | 0.014 | 40 (0.46) | 42 (0.49) | 0.003 |
| Skin infections | 508 (3.73) | 939 (3.19) | 0.030 | 319 (3.69) | 288 (3.33) | 0.019 |
| Erectile dysfunction | 2154 (15.82) | 4245 (14.43) | 0.039 | 1269 (14.67) | 1275 (14.74) | 0.002 |
| Diabetes with unspecified complication | 108 (0.79) | 258 (0.88) | 0.009 | 43 (0.50) | 49 (0.57) | 0.01 |
| Diabetes mellitus without mention of complications | 24 (0.18) | 35 (0.12) | 0.015 | 13 (0.15) | 15 (0.17) | 0.006 |
| Other comorbidities, n (%) | ||||||
| Hypertension | 7744 (56.87) | 18 044 (61.32) | 0.091 | 4772 (55.17) | 4783 (55.29) | 0.003 |
| Ischaemic heart disease | 1757 (12.90) | 5548 (18.85) | 0.163 | 1111 (12.84) | 1091 (12.61) | 0.007 |
| Acute myocardial infarction | 763 (5.60) | 2242 (7.62) | 0.081 | 489 (5.65) | 487 (5.63) | 0.001 |
| Stable angina | 821 (6.03) | 2838 (9.64) | 0.135 | 496 (5.73) | 481 (5.56) | 0.008 |
| Previous cardiac procedure | 476 (3.50) | 1444 (4.91) | 0.070 | 300 (3.47) | 297 (3.43) | 0.002 |
| History of CABG or PTCA | 209 (1.53) | 890 (3.02) | 0.100 | 137 (1.58) | 137 (1.58) | 0 |
| Any stroke | 350 (2.57) | 1492 (5.07) | 0.131 | 249 (2.88) | 236 (2.73) | 0.009 |
| Haemorrhagic stroke | 26 (0.19) | 122 (0.41) | 0.041 | 23 (0.27) | 19 (0.22) | 0.009 |
| Cerebrovascular procedure | 2 (0.01) | 3 (0.01) | 0.004 | 0 (0) | 1 (0.01) | 0.015 |
| CHF | 313 (2.30) | 1546 (5.25) | 0.155 | 213 (2.46) | 201 (2.32) | 0.009 |
| Peripheral vascular disease or surgery | 185 (1.36) | 627 (2.13) | 0.059 | 119 (1.38) | 108 (1.25) | 0.011 |
| Atrial fibrillation | 503 (3.69) | 2401 (8.16) | 0.190 | 353 (4.08) | 352 (4.07) | 0.001 |
| Other cardiac dysrhythmia | 26 (0.19) | 52 (0.18) | 0.003 | 13 (0.15) | 18 (0.21) | 0.014 |
| Oedema | 2135 (15.68) | 5739 (19.50) | 0.101 | 1269 (14.67) | 1296 (14.98) | 0.009 |
| COPD | 757 (5.56) | 2345 (7.97) | 0.096 | 512 (5.92) | 514 (5.94) | 0.001 |
| Asthma | 2279 (16.74) | 4205 (14.29) | 0.068 | 1352 (15.63) | 1348 (15.58) | 0.001 |
| Pneumonia | 740 (5.43) | 1814 (6.16) | 0.031 | 455 (5.26) | 452 (5.23) | 0.002 |
| Chronic kidney disease | 550 (4.04) | 6099 (20.73) | 0.524 | 404 (4.67) | 421 (4.87) | 0.009 |
| Chronic renal insufficiency | 54 (0.40) | 540 (1.84) | 0.137 | 40 (0.46) | 42 (0.49) | 0.003 |
| Chronic kidney disease stage 1‐2 | 420 (3.08) | 1188 (4.04) | 0.051 | 231 (2.67) | 236 (2.73) | 0.004 |
| Chronic kidney disease stage 3‐4 | 166 (1.22) | 1855 (6.30) | 0.270 | 127 (1.47) | 126 (1.46) | 0.001 |
| Hypertensive nephropathy | 1 (0.01) | 4 (0.01) | 0.006 | 0 (0) | 0 (0) | |
| Liver disease | 165 (1.21) | 343 (1.17) | 0.004 | 104 (1.20) | 116 (1.34) | 0.012 |
| Osteoarthritis | 2416 (17.74) | 6918 (23.51) | 0.143 | 1543 (17.84) | 1554 (17.97) | 0.003 |
| Other arthritis, arthropathies and musculoskeletal pain | 201 (1.48) | 545 (1.85) | 0.029 | 142 (1.64) | 149 (1.72) | 0.006 |
| Bone fractures | 1510 (11.09) | 3391 (11.52) | 0.014 | 933 (10.79) | 937 (10.83) | 0.001 |
| Falls | 321 (2.36) | 1270 (4.32) | 0.109 | 219 (2.53) | 217 (2.51) | 0.001 |
| Osteoporosis | 288 (2.12) | 1405 (4.77) | 0.146 | 200 (2.31) | 197 (2.28) | 0.002 |
| Hyperthyroidism | 114 (0.84) | 281 (0.95) | 0.012 | 62 (0.72) | 59 (0.68) | 0.004 |
| Hypothyroidism | 1372 (10.08) | 2988 (10.15) | 0.003 | 800 (9.25) | 803 (9.28) | 0.001 |
| Other disorders of the thyroid gland | 10 (0.07) | 17 (0.06) | 0.006 | 5 (0.06) | 6 (0.07) | 0.005 |
| Depression | 5147 (37.80) | 8801 (29.91) | 0.167 | 2996 (34.64) | 3040 (35.14) | 0.011 |
| Anxiety | 2239 (16.44) | 4492 (15.27) | 0.032 | 1408 (16.28) | 1450 (16.76) | 0.013 |
| Sleep disorder | 926 (6.80) | 920 (3.13) | 0.170 | 426 (4.92) | 409 (4.73) | 0.009 |
| Dementia | 85 (0.62) | 806 (2.74) | 0.165 | 69 (0.80) | 71 (0.82) | 0.003 |
| Delirium | 10 (0.07) | 51 (0.17) | 0.028 | 8 (0.09) | 8 (0.09) | 0 |
| Psychosis | 94 (0.69) | 234 (0.80) | 0.012 | 69 (0.80) | 76 (0.88) | 0.009 |
| Foot ulcer | 47 (0.35) | 91 (0.31) | 0.006 | 24 (0.28) | 26 (0.30) | 0.004 |
| Cellulitis or abscess of toe | 2 (0.01) | 4 (0.01) | 0.001 | 0 (0) | 0 (0) | |
| Imaging | 4079 (29.96) | 8883 (30.19) | 0.005 | 2511 (29.03) | 2509 (29.01) | 0.001 |
| Glaucoma or cataracts | 497 (3.65) | 1725 (5.86) | 0.104 | 307 (3.55) | 324 (3.75) | 0.01 |
Abbreviations: CABG, coronary artery bypass grafting; CHF, chronic heart failure; COPD, chronic obstructive pulmonary disease; DPP‐4, dipeptidyl peptidase‐4; PTCA, percutaneous transluminal coronary angioplasty; SD, standard deviation; SGLT2, sodium‐glucose cotransporter‐2; SMD, standardized mean difference.