Metformin and the Risk of Chronic Urticaria in Patients with Type 2 Diabetes
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population and Design
2.2. Procedures
2.3. Main Outcomes
2.4. Statistical Analysis
3. Results
3.1. Participants
3.2. Main Outcomes
3.3. Cumulative Duration of Metformin Use
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variable | Pre-Matched | Post-Matched | ||||
---|---|---|---|---|---|---|
Non-Metformin Users | Metformin Users | SMD § | Non-Metformin Users | Metformin Users | SMD § | |
n (%) | n (%) | n (%) | n (%) | |||
All | 40,476 | 116,262 | 0.2784 | 24,987 | 24,987 | 0.0020 |
Sex | 0.1221 | 0.0199 | ||||
Female | 20,381 (50.35) | 51,467 (44.27) | 11,981 (47.95) | 12,230 (48.95) | ||
Male | 20,095 (49.65) | 64,795 (55.73) | 13,006 (52.05) | 12,757 (51.05) | ||
Age group (year) | ||||||
20–39 | 3029 (7.48) | 9948 (8.56) | 0.0395 | 1949 (7.80) | 1736 (6.95) | 0.0326 |
40–59 | 15,986 (39.50) | 59,541 (51.21) | 0.2370 | 10,462 (41.87) | 10,185 (40.76) | 0.0225 |
60+ | 21,461 (53.02) | 46,773 (40.23) | 0.2585 | 12,576 (50.33) | 13,066 (52.29) | 0.0392 |
Age (year, mean ± SD) | 59.51 ± 12.50 | 56.27 ± 11.86 | 0.2665 | 58.85 ± 12.50 | 59.41 ± 12.30 | 0.0453 |
Comorbidities | ||||||
Obesity | 0.0008 | 0.0098 | ||||
No | 39,936 (98.67) | 114,700 (98.66) | 24,649 (98.65) | 24,620 (98.53) | ||
Yes | 540 (1.33) | 1562 (1.34) | 338 (1.35) | 367 (1.47) | ||
Smoking status | 0.0297 | 0.0015 | ||||
No | 39,724 (98.14) | 114,544 (98.52) | 24,561 (98.30) | 24,556 (98.28) | ||
Yes | 752 (1.86) | 1718 (1.48) | 426 (1.70) | 431 (1.72) | ||
Alcohol-related disorders | 0.0440 | 0.0029 | ||||
No | 39,188 (96.82) | 113,409 (97.55) | 24,189 (96.81) | 24,176 (96.75) | ||
Yes | 1288 (3.18) | 2853 (2.45) | 798 (3.19) | 811 (3.25) | ||
Hypertension | 0.0713 | 0.0542 | ||||
No | 16,440 (40.62) | 51,314 (44.14) | 9934 (39.76) | 9276 (37.12) | ||
Yes | 24,036 (59.38) | 64,948 (55.86) | 15,053 (60.24) | 15,711 (62.88) | ||
Dyslipidemia | 0.2041 | 0.0546 | ||||
No | 17,065 (42.16) | 60,802 (52.30) | 11,237 (44.97) | 10,561 (42.27) | ||
Yes | 23,411 (57.84) | 55,460 (47.70) | 13,750 (55.03) | 14,426 (57.73) | ||
Coronary artery disease | 0.2014 | 0.0378 | ||||
No | 28,037 (69.27) | 90,790 (78.09) | 17,813 (71.29) | 17,382 (69.56) | ||
Yes | 12,439 (30.73) | 25,472 (21.91) | 7174 (28.71) | 7605 (30.44) | ||
Stroke | 0.2054 | 0.0332 | ||||
No | 33,211 (82.05) | 103,727 (89.22) | 20,946 (83.83) | 20,636 (82.59) | ||
Yes | 7265 (17.95) | 12,535 (10.78) | 4041 (16.17) | 4351 (17.41) | ||
Heart failure | 0.1284 | 0.0111 | ||||
No | 37,635 (92.98) | 111,513 (95.92) | 23,350 (93.45) | 23,281 (93.17) | ||
Yes | 2841 (7.02) | 4749 (4.08) | 1637 (6.55) | 1706 (6.83) | ||
Peripheral arterial disease | 0.0841 | 0.0041 | ||||
No | 39,085 (96.56) | 113,864 (97.94) | 24,217 (96.92) | 24,199 (96.85) | ||
Yes | 1391 (3.44) | 2398 (2.06) | 770 (3.08) | 788 (3.15) | ||
Chronic kidney disease | 0.2572 | 0.0019 | ||||
No | 36,554 (90.31) | 112,328 (96.62) | 23,196 (92.83) | 23,208 (92.88) | ||
Yes | 3922 (9.69) | 3934 (3.38) | 1791 (7.17) | 1779 (7.12) | ||
Chronic obstructive pulmonary disease | 0.1964 | 0.0156 | ||||
No | 32,434 (80.13) | 101,549 (87.34) | 20,492 (82.01) | 20,341 (81.41) | ||
Yes | 8042 (19.87) | 14,713 (12.66) | 4495 (17.99) | 4646 (18.59) | ||
Rheumatoid arthritis | 0.0787 | 0.0009 | ||||
No | 39,455 (97.48) | 114,602 (98.57) | 24,480 (97.97) | 24,477 (97.96) | ||
Yes | 1021 (2.52) | 1660 (1.43) | 507 (2.03) | 510 (2.04) | ||
Systemic lupus erythematous | 0.0547 | 0.0077 | ||||
No | 40,310 (99.59) | 116,114 (99.87) | 24,914 (99.71) | 24,924 (99.75) | ||
Yes | 166 (0.41) | 148 (0.13) | 73 (0.29) | 63 (0.25) | ||
Liver cirrhosis | 0.0934 | 0.0130 | ||||
No | 39,274 (97.03) | 114,427 (98.42) | 24,360 (97.49) | 24,308 (97.28) | ||
Yes | 1202 (2.97) | 1835 (1.58) | 627 (2.51) | 679 (2.72) | ||
Cancers | 0.1492 | 0.0137 | ||||
No | 37,796 (93.38) | 112,335 (96.62) | 23,659 (94.69) | 23,581 (94.37) | ||
Yes | 2680 (6.62) | 3927 (3.38) | 1328 (5.31) | 1406 (5.63) | ||
Psychosis | 0.0434 | 0.0059 | ||||
No | 39,507 (97.61) | 114,199 (98.23) | 24,438 (97.80) | 24,416 (97.71) | ||
Yes | 969 (2.39) | 2063 (1.77) | 549 (2.20) | 571 (2.29) | ||
Depression | 0.1390 | 0.0070 | ||||
No | 37,855 (93.52) | 112,237 (96.54) | 23,685 (94.79) | 23,646 (94.63) | ||
Yes | 2621 (6.48) | 4025 (3.46) | 1302 (5.21) | 1341 (5.37) | ||
Dementia | 0.0886 | 0.0073 | ||||
No | 40,185 (99.28) | 116,099 (99.86) | 24,871 (99.54) | 24,883 (99.58) | ||
Yes | 291 (0.72) | 163 (0.14) | 116 (0.46) | 104 (0.42) | ||
Charlson Comorbidity Index | ||||||
0 | 26,627 (65.78) | 92,391 (79.47) | 0.3106 | 17,269 (69.11) | 16,821 (67.32) | 0.0385 |
1 | 5201 (12.85) | 12,028 (10.35) | 0.0783 | 3193 (12.78) | 3412 (13.66) | 0.0259 |
2+ | 8648 (21.37) | 11,843 (10.19) | 0.3104 | 4525 (18.11) | 4754 (19.03) | 0.0236 |
Diabetes Complications Severity Index | ||||||
0 | 12,926 (31.93) | 54,792 (47.13) | 0.3146 | 8964 (35.87) | 8036 (32.16) | 0.0785 |
1 | 7530 (18.60) | 21,500 (18.49) | 0.0029 | 4692 (18.78) | 4936 (19.75) | 0.0248 |
2+ | 20,020 (49.46) | 39,970 (34.38) | 0.3093 | 11,331 (45.35) | 12,015 (48.09) | 0.0549 |
Medications | ||||||
Numbers of oral antidiabetic drugs | ||||||
<2 | 39,780 (98.28) | 111,718 (96.09) | 0.1327 | 24,393 (97.62) | 24,264 (97.11) | 0.0322 |
2–3 | 690 (1.70) | 4508 (3.88) | 0.1322 | 589 (2.36) | 716 (2.87) | 0.0319 |
>3 | 6 (0.01) | 36 (0.03) | 0.0107 | 5 (0.02) | 7 (0.03) | 0.0052 |
Glucagon-like peptide-1 receptor agonists | 0.0059 | 0.0052 | ||||
No | 40,476 (100.00) | 116,262 (100.00) | 24,987 (100.00) | 24,987 (100.00) | ||
Yes | ||||||
Insulins | 0.2107 | 0.0297 | ||||
No | 31,443 (77.68) | 99,730 (85.78) | 19,659 (78.68) | 19,352 (77.45) | ||
Yes | 9033 (22.32) | 16,532 (14.22) | 5328 (21.32) | 5635 (22.55) | ||
Non-steroidal anti-inflammatory drugs | 0.8256 | 0.0937 | ||||
No | 6349 (15.69) | 60,183 (51.76) | 6081 (24.34) | 5106 (20.43) | ||
Yes | 34,127 (84.31) | 56,079 (48.24) | 18,906 (75.66) | 19,881 (79.57) | ||
Statins | 0.2569 | 0.0430 | ||||
No | 28,760 (71.05) | 95,178 (81.87) | 18,623 (74.53) | 18,149 (72.63) | ||
Yes | 11,716 (28.95) | 21,084 (18.13) | 6364 (25.47) | 6838 (27.37) | ||
Aspirin | 0.2706 | 0.0342 | ||||
No | 28,799 (71.15) | 95,881 (82.47) | 18,291 (73.20) | 17,909 (71.67) | ||
Yes | 11,677 (28.85) | 20,381 (17.53) | 6696 (26.80) | 7078 (28.33) | ||
Duration of T2D (year) | 4.09 ± 3.68 | 2.08 ± 3.13 | 0.5901 | 3.44 ± 3.29 | 3.54 ± 3.70 | 0.0293 |
HbA1c check-up > 2 per year | 1.3409 | 0.0466 | ||||
No | 35,846 (88.56) | 39,944 (34.36) | 20,383 (81.57) | 19,923 (79.73) | ||
Yes | 4630 (11.44) | 76,318 (65.64) | 4604 (18.43) | 5064 (20.27) |
Variable | Non-Metformin Users | Metformin Users | Crude HR | Adjusted HR # | ||||||
---|---|---|---|---|---|---|---|---|---|---|
Event | Person-Years | IR * | Event | Person-Years | IR * | HR (95% CI) | p-Value | HR (95% CI) | p-Value | |
New-onset chronic urticaria | 496 | 142,255 | 3.49 | 819 | 158,517 | 5.17 | 1.49 (1.33, 1.66) | <0.0001 | 1.56 (1.39, 1.74) | <0.0001 |
Severe chronic urticaria | 9 | 145,454 | 0.06 | 4 | 164,410 | 0.02 | 0.39 (0.12, 1.27) | 0.1177 | 0.40 (0.12, 1.30) | 0.1264 |
Hospitalization for chronic urticaria | 19 | 145,399 | 0.13 | 33 | 164,297 | 0.2 | 1.53 (0.87, 2.70) | 0.1369 | 1.45 (0.82, 2.56) | 0.2009 |
Variable | Event | Person-Years | IR * | Crude HR | Adjusted HR # | ||
---|---|---|---|---|---|---|---|
HR (95% CI) | p-Value | HR (95% CI) | p-Value | ||||
New-onset chronic urticaria | |||||||
Non-metformin users | 496 | 142,255 | 3.49 | 1 (Reference) | 1 (Reference) | ||
Metformin users | |||||||
1–31 days/years | 177 | 42,992 | 4.12 | 1.19 (1.00, 1.41) | 0.0515 | 1.15 (0.97, 1.37) | 0.1051 |
32–88 days/years | 164 | 39,889 | 4.11 | 1.18 (0.99, 1.41) | 0.0599 | 1.21 (1.01, 1.44) | 0.0346 |
89–145 days/years | 142 | 39,230 | 3.62 | 1.04 (0.86, 1.25) | 0.6950 | 1.17 (0.97, 1.41) | 0.1021 |
>145 days/years | 336 | 36,405 | 9.23 | 2.67 (2.32, 3.07) | <0.0001 | 3.02 (2.62, 3.48) | <0.0001 |
Severe chronic urticaria | |||||||
Non-metformin users | 9 | 145,454 | 0.06 | 1 (Reference) | 1 (Reference) | ||
Metformin users | |||||||
1–31 days/years | 4 | 164,410 | 0.07 | 1.10 (0.30, 4.07) | 0.8867 | 1.15 (0.30, 4.43) | 0.8344 |
32–88 days/years | 0.00 | NA | NA | NA | NA | ||
89–145 days/years | 0.00 | NA | NA | NA | NA | ||
>145 days/years | 0.03 | 0.42 (0.05, 3.31) | 0.4097 | 0.42 (0.05, 3.36) | 0.4131 | ||
Hospitalization for chronic urticaria | |||||||
Non-metformin users | 19 | 145,399 | 0.13 | 1 (Reference) | 1 (Reference) | ||
Metformin users | |||||||
1–31 days/years | 9 | 43,815 | 0.21 | 1.57 (0.71, 3.47) | 0.2649 | 1.38 (0.62, 3.08) | 0.4274 |
32–88 days/years | 7 | 41,090 | 0.17 | 1.30 (0.55, 3.09) | 0.5539 | 1.25 (0.53, 2.98) | 0.6124 |
89–145 days/years | 5 | 40,744 | 0.12 | 0.94 (0.35, 2.52) | 0.9009 | 0.94 (0.35, 2.53) | 0.8958 |
>145 days/years | 12 | 38,648 | 0.31 | 2.37 (1.15, 4.89) | 0.0191 | 2.27 (1.09, 4.74) | 0.0284 |
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Yen, F.-S.; Hsu, C.-C.; Hu, K.-C.; Hung, Y.-T.; Hsu, C.Y.; Wei, J.C.-C.; Hwu, C.-M. Metformin and the Risk of Chronic Urticaria in Patients with Type 2 Diabetes. Int. J. Environ. Res. Public Health 2022, 19, 11045. https://doi.org/10.3390/ijerph191711045
Yen F-S, Hsu C-C, Hu K-C, Hung Y-T, Hsu CY, Wei JC-C, Hwu C-M. Metformin and the Risk of Chronic Urticaria in Patients with Type 2 Diabetes. International Journal of Environmental Research and Public Health. 2022; 19(17):11045. https://doi.org/10.3390/ijerph191711045
Chicago/Turabian StyleYen, Fu-Shun, Chih-Cheng Hsu, Kai-Chieh Hu, Yu-Tung Hung, Chung Y. Hsu, James Cheng-Chung Wei, and Chii-Min Hwu. 2022. "Metformin and the Risk of Chronic Urticaria in Patients with Type 2 Diabetes" International Journal of Environmental Research and Public Health 19, no. 17: 11045. https://doi.org/10.3390/ijerph191711045