Background
Methods
Data source
Study population
Definition of variables
Statistical analysis
Results
Total | Severe hypoglycemia | Number of severe hypoglycemia | |||||||
---|---|---|---|---|---|---|---|---|---|
No | Yes | P value | No | 1 | 2 | 3 or more | P for trend | ||
Total | 1,568,097 | 1,548,437 (98.7) | 19,660 (1.3) | 1,548,437 (98.7) | 15,992 (1.0) | 2543 (0.2) | 1125 (0.1) | ||
Age (%) | < 0.001 | < 0.001 | |||||||
30–49 years | 360,764 (23.0) | 358,253 (23.1) | 2511 (12.8) | 358,253 (23.1) | 1985 (12.4) | 309 (12.2) | 217 (19.3) | ||
50–64 years | 681,133 (43.4) | 675,499 (43.6) | 5634 (28.7) | 675,499 (43.6) | 4715 (29.5) | 627 (24.7) | 292 (26.0) | ||
65– years | 526,200 (33.6) | 514,685 (33.2) | 11,515 (58.6) | 514,685 (33.2) | 9292 (58.1) | 1607 (63.2) | 616 (54.8) | ||
Sex (male) | 857,078 (54.7) | 847,922 (54.8) | 9156 (46.6) | < 0.001 | 847,922 (54.8) | 7394 (46.2) | 1181 (46.4) | 581 (51.6) | < 0.001 |
Urban (%) | 737,077 (47.0) | 729,017 (47.1) | 8060 (41.0) | < 0.001 | 729,017 (47.1) | 6664 (41.7) | 980 (38.6) | 416 (37.0) | < 0.001 |
Socioeconomic status (%) | < 0.001 | < 0.001 | |||||||
Lower 30% | 533,293 (34.0) | 524,963 (33.9) | 8330 (42.4) | 524,963 (33.9) | 6530 (40.8) | 1179 (46.4) | 621 (55.2) | ||
Mid 40% | 486,963 (31.1) | 481,579 (31.1) | 5384 (27.4) | 481,579 (31.1) | 4508 (28.2) | 640 (25.2) | 236 (21.0) | ||
Upper 30% | 547,841 (34.9) | 541,895 (35.0) | 5946 (30.2) | 541,895 (35.0) | 4954 (31.0) | 724 (28.5) | 268 (23.8) | ||
Medication (%) | |||||||||
Insulin | 224,761 (14.3) | 215,976 (14.0) | 8785 (44.7) | < 0.001 | 215,976 (14.0) | 6800 (42.5) | 1316 (51.8) | 669 (59.5) | < 0.001 |
Sulfonylurea | 1223,327 (78.0) | 1,208,722 (78.1) | 14,605 (74.3) | < 0.001 | 1,208,722 (78.1) | 12,043 (75.3) | 1827 (71.8) | 735 (65.3) | < 0.001 |
Metformin | 1,110,628 (70.8) | 1,097,712 (70.9) | 12,916 (65.7) | < 0.001 | 1,097,712 (70.9) | 10,562 (66.1) | 1664 (65.4) | 690 (61.3) | < 0.001 |
Meglitinide | 74,406 (4.7) | 72,350 (4.67) | 2056 (10.5) | < 0.001 | 72,350 (4.67) | 1571 (9.8) | 346 (13.6) | 139 (12.4) | < 0.001 |
Thiazolidinedione | 212,955 (13.6) | 210,178 (13.6) | 2777 (14.1) | 0.025 | 210,178 (13.6) | 2274 (14.2) | 344 (13.5) | 159 (14.1) | 0.115 |
DPP4 inhibitor | 137,010 (8.7) | 135,428 (8.8) | 1582 (8.1) | 0.001 | 135,428 (8.8) | 1265 (7.9) | 224 (8.8) | 93 (8.3) | 0.003 |
Acarbose | 345,942 (22.1) | 339,257 (21.9) | 6685 (34.0) | < 0.001 | 339,257 (21.9) | 5330 (33.3) | 968 (38.1) | 387 (34.4) | < 0.001 |
Hypertension (%) | 872,321 (55.6) | 858,893 (55.5) | 13,428 (68.3) | < 0.001 | 858,893 (55.5) | 10,895 (68.1) | 1778 (69.9) | 755 (67.1) | < 0.001 |
Dyslipidemia (%) | 593,295 (37.8) | 586,718 (37.9) | 6577 (33.5) | < 0.001 | 586,718 (37.9) | 5496 (34.4) | 791 (31.1) | 290 (25.8) | < 0.001 |
COPD (%) | 52,126 (3.3) | 51,244 (3.3) | 882 (4.5) | < 0.001 | 51,244 (3.3) | 712 (4.5) | 124 (4.9) | 46 (4.1) | < 0.001 |
Malignancy (%) | 17,121 (1.1) | 16,738 (1.1) | 383 (2.0) | < 0.001 | 16,738 (1.1) | 312 (2.0) | 52 (2.0) | 19 (1.7) | < 0.001 |
Liver cirrhosis (%) | 4072 (0.3) | 3984 (0.3) | 88 (0.5) | < 0.001 | 3984 (0.3) | 71 (0.4) | 12 (0.5) | 5 (0.4) | < 0.001 |
ESRD (%) | 962 (0.1) | 862 (0.1) | 100 (0.5) | < 0.001 | 862 (0.1) | 79 (0.5) | 13 (0.5) | 8 (0.7) | < 0.001 |
Outcome | Number of severe hypoglycemia | N | Event | Incidence rate (per 1000 patient-years) | HR (95% CI) | P for trend | ||
---|---|---|---|---|---|---|---|---|
Crude | Sex- and age adjusted | Multivariablea | ||||||
Myocardial infarction | 0 | 1,548,437 | 58,529 | 6.7 | Reference | Reference | Reference | < 0.001 |
1 | 15,992 | 945 | 12.1 | 2.36 (2.21–2.51) | 1.83 (1.72–1.96) | 1.56 (1.46–1.64) | ||
2 | 2543 | 182 | 16.1 | 3.12 (2.70–3.61) | 2.31 (1.99–2.67) | 1.86 (1.61–2.15) | ||
3 or more | 1125 | 72 | 15.5 | 2.99 (2.97–3.77) | 2.39 (1.90–3.01) | 1.86 (1.48–2.35) | ||
Stroke | 0 | 1,548,437 | 58,529 | 6.7 | Reference | Reference | Reference | < 0.001 |
1 | 15,992 | 1304 | 16.9 | 2.53 (2.40–2.67) | 1.78 (1.68–1.88) | 1.54 (1.46–1.63) | ||
2 | 2543 | 228 | 20.2 | 3.03 (2.66–3.45) | 1.97 (1.73–2.24) | 1.62 (1.42–1.84) | ||
3 or more | 1125 | 115 | 24.9 | 3.74 (3.11–4.49) | 2.69 (2.25–3.24) | 2.14 (1.78–2.57) | ||
Heart failure | 0 | 1,548,437 | 52,485 | 6.0 | Reference | Reference | Reference | < 0.001 |
1 | 15,992 | 1423 | 18.4 | 3.13 (2.97–3.30) | 2.09 (1.99–2.21) | 1.68 (1.60–1.78) | ||
2 | 2543 | 283 | 25.2 | 4.33 (3.85–4.87) | 2.66 (2.36–2.99) | 2.00 (1.78–2.25) | ||
3 or more | 1125 | 139 | 30.5 | 5.31 (4.49–6.27) | 3.65 (3.09–4.31) | 2.59 (2.19–3.06) | ||
All-cause death | 0 | 1,548,437 | 146,332 | 16.5 | Reference | Reference | Reference | < 0.001 |
1 | 15,992 | 5058 | 63.3 | 3.88 (3.77–3.99) | 2.46 (2.39–2.53) | 1.98 (1.93–2.04) | ||
2 | 2543 | 1074 | 91.6 | 5.63 (5.31–3.98) | 3.24 (3.05–3.44) | 2.39 (2.25–2.53) | ||
3 or more | 1125 | 572 | 119.0 | 7.37 (6.79–8.00) | 4.73 (4.35–5.13) | 3.28 (3.02–3.56) |