Impact of Metformin Use on Survival in Patients with Gastric Cancer and Diabetes Mellitus Following Gastrectomy
Abstract
1. Introduction
2. Materials and Methods
3. Results
4. Discussion
5. Limitations
6. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Parameters | Total Patients n = 2400 | Patients with Diabetes (n = 651) | p-Value | ||||
---|---|---|---|---|---|---|---|
Metformin Users n = 248 | Non-Metformin Users n = 403 | ||||||
Gender | 0.8260 | ||||||
Male | 1515 | (63.13) | 148 | (59.68) | 244 | (60.55) | |
Female | 885 | (36.88) | 100 | (40.32) | 159 | (39.45) | |
Age (Years) | 0.0006 | ||||||
Mean ± Standard Deviation | 63.37 ± 13.17 | 65.49 ± 10.48 | 68.50 ± 10.94 | ||||
Charlson Comorbidity Index Score | |||||||
Mean ± Standard Deviation | 5.42 ± 3.20 | 5.69 ± 3.43 | 6.03 ± 3.45 | 0.2090 | |||
≤6 | 1333 | (55.54) | 160 | (64.52) | 213 | (52.85) | 0.0035 |
>6 | 1067 | (44.46) | 88 | (35.48) | 190 | (47.15) | |
Glycohaemoglobin (HbA1c, %) | <0.0001 | ||||||
Mean ± Standard Deviation | 7.34 ± 1.39 | 6.33 ± 1.01 | |||||
Glucose, AC (mg/dL) | <0.0001 | ||||||
Mean ± Standard Deviation | 149.00 ± 49.27 | 116.33 ± 40.9 | |||||
Type of Gastrectomy | <0.0001 | ||||||
Total Gastrectomy | 646 | (26.92) | 37 | (14.92) | 122 | (30.27) | |
Partial Gastrectomy | 1754 | (73.08) | 211 | (85.08) | 281 | (69.73) | |
Number of Lymph Node Retrieved | 0.8016 | ||||||
Mean ± Standard Deviation | 29.81 ± 16.07 | 29.17 ± 17.36 | 28.84 ± 15.94 | ||||
Tumour Size (cm) | 0.0001 | ||||||
Mean ± Standard Deviation | 4.30 ± 2.96 | 3.49 ± 2.38 | 4.32 ± 3.00 | ||||
Differentiation | 0.0012 | ||||||
Yes | 1395 | (58.13) | 111 | (44.76) | 233 | (57.82) | |
No | 1005 | (41.88) | 137 | (55.24) | 170 | (42.18) | |
Resection Margins | 0.0117 | ||||||
Negative | 2236 | (93.17) | 242 | (97.58) | 375 | (93.05) | |
Positive | 164 | (6.83) | 6 | (2.42) | 28 | (6.95) | |
Stage (AJCC 7th ed.) | <0.0001 | ||||||
I | 746 | (31.08) | 116 | (46.77) | 123 | (30.52) | |
II | 460 | (19.17) | 49 | (19.76) | 88 | (21.84) | |
III | 1194 | (49.75) | 83 | (33.47) | 192 | (47.64) | |
Vascular Invasion | 0.2553 | ||||||
No | 2091 | (87.13) | 224 | (90.32) | 361 | (89.58) | |
Yes | 269 | (11.21) | 19 | (7.66) | 39 | (9.68) | |
Unknown | 40 | (1.67) | 5 | (2.02) | 3 | (0.74) | |
Lymphatic Invasion | 0.0026 | ||||||
No | 1197 | (49.88) | 154 | (62.10) | 200 | (49.63) | |
Yes | 1168 | (48.67) | 89 | (35.89) | 199 | (49.38) | |
Unknown | 35 | (1.46) | 5 | (2.02) | 4 | (0.99) | |
Perineural Invasion | 0.0009 | ||||||
No | 1385 | (57.71) | 175 | (70.56) | 232 | (57.57) | |
Yes | 975 | (40.63) | 67 | (27.02) | 166 | (41.19) | |
Unknown | 40 | (1.67) | 6 | (2.42) | 5 | (1.24) | |
Adjuvant Chemotherapy | 0.5224 | ||||||
No | 951 | (39.63) | 119 | (47.98) | 183 | (45.41) | |
Yes | 1449 | (60.38) | 129 | (52.02) | 220 | (54.59) | |
Chemotherapy Regimen | 0.6432 | ||||||
Fluoropyrimidine-Based | 1338 | (95.79) | 126 | (97.67) | 211 | (95.91) | |
Platinum-Based | 50 | (3.45) | 2 | (1.55) | 7 | (3.18) | |
Others | 11 | (0.76) | 1 | (0.78) | 2 | (0.91) | |
Chemotherapy Duration (Months) | |||||||
Mean ± Standard Deviation | 7.98 ± 6.74 | 8.10 ± 6.87 | 7.92 ± 6.68 | 0.8340 | |||
Other Hypoglycaemic Medication | |||||||
Sulfonylurea | 346 | (14.42) | 174 | (70.16) | 150 | (37.22) | <0.0001 |
Meglitinide | 37 | (1.54) | 19 | (7.66) | 18 | (4.47) | 0.0873 |
α-Glucosidase Inhibitor | 42 | (1.75) | 25 | (10.08) | 17 | (4.22) | 0.0031 |
Thiazolidinedione | 52 | (2.17) | 33 | (13.31) | 19 | (4.71) | <0.0001 |
Insulin | 320 | (13.33) | 149 | (60.08) | 124 | (30.77) | <0.0001 |
Recurrence Pattern | 0.0002 | ||||||
No | 1412 | (58.83) | 191 | (77.02) | 259 | (64.27) | |
Locoregional | 235 | (23.79) | 22 | (8.87) | 27 | (6.70) | |
Peritoneal | 355 | (35.93) | 14 | (5.65) | 53 | (13.15) | |
Hemaetogenous | 398 | (40.28) | 21 | (8.47) | 64 | (15.88) |
Prognosis | Stage I–III | Stage I | Stage II | Stage III | ||||
---|---|---|---|---|---|---|---|---|
Non-Metformin Users (n = 403) | Metformin Users (n = 248) | Non-Metformin Users (n = 123) | Metformin Users (n = 116) | Non-Metformin Users (n = 88) | Metformin Users (n = 49) | Non-Metformin Users (n = 192) | Metformin Users (n = 83) | |
Gastric Cancer Recurrence | ||||||||
Number of Patients | 144 (37.02) a | 57 (24.89) a | 8 (6.78) b | 9 (8.49) b | 21 (25.00) c | 10 (21.28) c | 115 (61.50) d | 38 (50.00) d |
Crude HR (95% CI) | 1 | 0.60 (0.45–0.82) * | 1 | 1.27 (0.49–3.27) | 1 | 0.84 (0.40–1.76) | 1 | 0.68 (0.48–0.96) * |
Adjusted HR (95% CI) e | 1 | 0.61 (0.43–0.88) * | 1 | 1.45 (0.32–6.58) | 1 | 0.44 (0.16–1.21) | 1 | 0.55 (0.36–0.83) * |
All-Cause Death | ||||||||
Number of Patients | 251 (62.28) | 119 (47.98) | 48 (39.02) | 35 (30.17) | 45 (51.14) | 24 (48.98) | 158 (82.29) | 60 (72.29) |
Crude HR (95% CI) | 1 | 0.63 (0.51–0.79) * | 1 | 0.74 (0.48–1.14) | 1 | 0.90 (0.55–1.47) | 1 | 0.64 (0.47–0.86) * |
Adjusted HR (95% CI) e | 1 | 0.61 (0.47–0.79) * | 1 | 0.69 (0.37–1.28) | 1 | 0.95 (0.45–2.00) | 1 | 0.52 (0.38–0.73) * |
Death from Gastric Cancer | ||||||||
Number of Patients | 139 (34.49) | 59 (23.79) | 9 (7.32) | 8 (6.90) | 17 (19.32) | 11 (22.45) | 113 (58.85) | 40 (48.19) |
Crude HR (95% CI) | 1 | 0.57 (0.42–0.77) * | 1 | 0.90 (0.35–2.33) | 1 | 1.09 (0.51–2.34) | 1 | 0.59 (0.41–0.85) * |
Adjusted HR (95% CI) e | 1 | 0.54 (0.38–0.77) * | 1 | 1.70 (0.45–6.47) | 1 | 0.47 (0.16–1.40) | 1 | 0.45 (0.30–0.68) * |
Death from Other Reasons | ||||||||
Number of Patients | 112 (27.79) | 60 (24.19) | 39 (31.71) | 27 (23.28) | 28 (31.82) | 13 (26.53) | 45 (23.44) | 20 (24.10) |
Crude HR (95% CI) | 1 | 0.71 (0.52–0.97) * | 1 | 0.74 (0.45–1.21) | 1 | 0.73 (0.38–1.42) | 1 | 0.76 (0.44–1.29) |
Adjusted HR (95% CI) e | 1 | 0.75 (0.51–1.11) | 1 | 0.53 (0.27–1.03) | 1 | 2.35 (0.99–5.58) | 1 | 0.71 (0.37–1.36) |
Prognosis | Stage I–III | Stage I | Stage II | Stage III | ||||
---|---|---|---|---|---|---|---|---|
without DM (n = 1749) | with DM (n = 651) | without DM (n = 507) | with DM (n = 239) | without DM (n = 323) | with DM (n = 137) | without DM (n = 919) | with DM (n = 275) | |
Gastric Cancer Recurrence | ||||||||
Number of Patients | 787 (44.16) a | 201 (32.52) a | 37 (7.09%) b | 17 (7.59) b | 99 (30.09) c | 31 (23.66) c | 651 (69.92) d | 153 (58.17) d |
Crude HR (95% CI) | 1 | 0.67 (0.57–0.78) * | 1 | 1.06 (0.60–1.88) | 1 | 0.77 (0.52–1.16) | 1 | 0.71 (0.60–0.84) * |
Adjusted HR (95% CI) e | 1 | 0.67 (0.54–0.82) * | 1 | 0.94 (0.48–1.86) | 1 | 0.51 (0.30–0.86) * | 1 | 0.68 (0.53–0.87) * |
All-Cause Death | ||||||||
Number of Patients | 1047 (59.86) | 370 (56.84) | 152 (29.98) | 83 (34.73) | 151 (46.75) | 69 (50.36) | 744 (80.96) | 218 (79.27) |
Crude HR (95% CI) | 1 | 0.90 (0.80–1.01) | 1 | 1.22 (0.93–1.59) | 1 | 1.10 (0.83–1.47) | 1 | 0.93 (0.80–1.08) |
Adjusted HR (95% CI) e | 1 | 0.70 (0.59–0.82) * | 1 | 0.78 (0.55–1.12) | 1 | 0.51 (0.35–0.74) * | 1 | 0.73 (0.59–0.90) * |
Death from Gastric Cancer | ||||||||
Number of Patients | 760 (43.45) | 198 (30.41) | 31 (6.11) | 17 (7.11) | 91 (28.17) | 28 (20.44) | 638 (69.42) | 153 (55.64) |
Crude HR (95% CI) | 1 | 0.66 (0.57–0.78) * | 1 | 1.18 (0.65–1.13) | 1 | 0.76 (0.50–1.16) | 1 | 0.76 (0.64–0.91) * |
Adjusted HR (95% CI) e | 1 | 0.62 (0.50–0.77) * | 1 | 0.97 (0.47–2.02) | 1 | 0.36 (0.19–0.67) * | 1 | 0.64 (0.50–0.82) * |
Death from Other Reasons | ||||||||
Number of Patients | 287 (16.41) | 172 (26.42) | 121 (23.87) | 66 (27.62) | 60 (18.58) | 41 (29.93) | 106 (11.53) | 65 (23.64) |
Crude HR (95% CI) | 1 | 1.50 (1.24–1.81) * | 1 | 1.23 (0.91–1.65) | 1 | 1.61 (1.08–2.39) * | 1 | 1.89 (1.39–2.58) * |
Adjusted HR (95% CI) e | 1 | 0.86 (0.67–1.10) | 1 | 0.73 (0.48–1.09) | 1 | 0.64 (0.38–1.09) | 1 | 1.26 (0.83–1.92) |
Prognosis | Non-Metformin Users (n = 192) | Metformin ≤ 1000 mg/day (n = 32) | Metformin > 1000 mg/day (n = 51) |
---|---|---|---|
Gastric Cancer Recurrence | |||
Number of Patients | 115 (61.50) a | 12 (41.38) a | 26 (55.32) a |
Crude HR (95% CI) | 1 | 0.52 (0.30–0.90) * | 0.79 (0.53–1.18) |
Adjusted HR (95% CI) b | 1 | 0.46 (0.24–0.88) * | 0.61 (0.39–0.94) * |
All-Cause Death | |||
Number of Patients | 158 (82.29) | 20 (62.50) | 40 (78.43) |
Crude HR (95% CI) | 1 | 0.51 (0.32–0.81) * | 0.73 (0.52–1.03) |
Adjusted HR (95% CI) b | 1 | 0.43 (0.28–0.65) * | 0.62 (0.46–0.85) * |
Death from Gastric Cancer | |||
Number of Patients | 113 (58.85) | 11 (34.38) | 29 (56.86) |
Crude HR (95% CI) | 1 | 0.39 (0.21–0.73) * | 0.74 (0.49–1.11) |
Adjusted HR (95% CI) b | 1 | 0.34 (0.19–0.60) * | 0.59 (0.41–0.87) * |
Death from Other Reasons | |||
Number of Patients | 45 (23.44) | 9 (28.13) | 11 (21.57) |
Crude HR (95% CI) | 1 | 0.82 (0.40–1.68) | 0.72 (0.37–1.39) |
Adjusted HR (95% CI) b | 1 | 0.69 (0.31–1.52) | 0.77 (0.39–1.53) |
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Chung, W.-S.; Le, P.-H.; Kuo, C.-J.; Chen, T.-H.; Kuo, C.-F.; Chiou, M.-J.; Chou, W.-C.; Yeh, T.-S.; Hsu, J.-T. Impact of Metformin Use on Survival in Patients with Gastric Cancer and Diabetes Mellitus Following Gastrectomy. Cancers 2020, 12, 2013. https://doi.org/10.3390/cancers12082013
Chung W-S, Le P-H, Kuo C-J, Chen T-H, Kuo C-F, Chiou M-J, Chou W-C, Yeh T-S, Hsu J-T. Impact of Metformin Use on Survival in Patients with Gastric Cancer and Diabetes Mellitus Following Gastrectomy. Cancers. 2020; 12(8):2013. https://doi.org/10.3390/cancers12082013
Chicago/Turabian StyleChung, Wai-Shan, Po-Hsien Le, Chiang-Jung Kuo, Tsung-Hsing Chen, Chang-Fu Kuo, Meng-Jiun Chiou, Wen-Chi Chou, Ta-Sen Yeh, and Jun-Te Hsu. 2020. "Impact of Metformin Use on Survival in Patients with Gastric Cancer and Diabetes Mellitus Following Gastrectomy" Cancers 12, no. 8: 2013. https://doi.org/10.3390/cancers12082013
APA StyleChung, W.-S., Le, P.-H., Kuo, C.-J., Chen, T.-H., Kuo, C.-F., Chiou, M.-J., Chou, W.-C., Yeh, T.-S., & Hsu, J.-T. (2020). Impact of Metformin Use on Survival in Patients with Gastric Cancer and Diabetes Mellitus Following Gastrectomy. Cancers, 12(8), 2013. https://doi.org/10.3390/cancers12082013