Metformin Use is Associated with Improved Survival in Patients undergoing Resection for Pancreatic Cancer

Marcelo Cerullo1, Faiz Gani1, Sophia Y. Chen1, Joe Canner1, Timothy M. Pawlik1

1Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.

Supplemental Table 1.Baseline clinical and demographic characteristics of patients undergoing surgery for pancreatic cancer.

Supplemental Table 2. Results from Cox proportional hazards regression analysis in subset of patients who underwent adjuvant therapy.

Supplemental Figure 1. Complementary log-log plots for strata of metformin use.

Supplemental Table 1.Baseline clinical and demographic characteristics of patients undergoing surgery for pancreatic cancer.

Characteristic / Surgery only / Surgery + chemoradiation / Surgery + chemotherapy / Surgery +
radiation therapy / Total
Male (%) / 788 (44.0) / 446 (54.9) / 353 (53.9) / 74 (52.9) / 1,661 (48.9)
Age, mean (SD) / 52.7 (10.3) / 55.9 (6.5) / 55.9 (7.3) / 55.4 (7.7) / 54.2 (9.1)
Region (%)
Northeast / 393 (21.9) / 177 (21.8) / 163 (24.9) / 23 (16.4) / 756 (22.2)
North Central / 390 (21.8) / 205 (25.2) / 167 (25.5) / 31 (22.1) / 793 (23.3)
South / 661 (36.9) / 300 (36.9) / 206 (31.5) / 61 (43.6) / 1,228 (36.1)
West / 313 (17.5) / 110 (13.5) / 109 (16.6) / 10 (1.5) / 552 (16.2)
Unknown / 35 (1.9) / 21 (2.6) / 10 (1.5) / 5 (3.6) / 71 (2.1)
Charlson co-morbidity index, (%)
0 / 309 (17.2) / 5 (0.6) / 14 (2.1) / 3 (2.1) / 331 (9.7)
1 / 104 (5.8) / 2 (0.3) / 3 (0.5) / 0 (0.0) / 109 (3.2)
2 / 739 (41.2) / 285 (35.1) / 204 (31.2) / 63 (45.0) / 1,291 (38.0)
3+ / 640 (35.7) / 521 (64.1) / 434 (66.3) / 74 (52.9) / 1,669 (49.1)
Diabetes diagnosis at surgery(%) / 305 (17.0) / 188 (23.1) / 152 (23.2) / 21 (15.0) / 666 (19.6)
Lymph node involvement (%) / 322 (18.0) / 374 (46.0) / 308 (47.0) / 55 (39.3) / 1059 (31.2)

Supplemental Table 2. Results from Cox proportional hazards regression analysis in patients who underwent adjuvant therapy.

Base model / Model including interaction between treatment group and metformin use
HR (95% CI) / p-value / HR (95% CI) / p-value
Metformin use / 0.81 (0.64 – 1.02) / 0.073 / 0.69 (0.50 – 0.97) / 0.030
Age / 1.03 (1.02 – 1.04) / <0.001 / 1.03 (1.02 – 1.04) / 0.001
Sex
Male / Reference / Reference
Female / 1.01 (0.87 – 1.16) / 0.941 / 1.01 (0.87 – 1.17) / 0.916
Region
Northeast / Reference / Reference
North Central / 1.01 (0.82 – 1.26) / 0.906 / 1.01 (0.82 – 1.26) / 0.898
South / 1.18 (0.97 – 1.43) / 0.107 / 1.18 (0.97 – 1.44) / 0.099
West / 1.08 (0.85 – 1.38) / 0.533 / 1.08 (0.84 – 1.38) / 0.536
Unknown / 2.03 (1.26 – 3.27) / 0.004 / 2.01 (1.25 – 3.26) / 0.004
Lymph node involvement / 1.11 (0.90 – 1.38) / 0.324 / 1.13 (0.91 – 1.40) / 0.276
Diabetes diagnosis at surgery / 1.19 (0.97 – 1.46) / 0.103 / 1.20 (0.97 – 1.47) / 0.091
Charlson co-morbidity index
0 / Reference / Reference
1 / 0.46 (0.06 – 3.75) / 0.467 / 0.46 (0.06 – 3.70) / 0.459
2 / 1.25 (0.59 – 2.67) / 0.560 / 1.26 (0.59 – 2.67) / 0.558
3+ / 1.51 (0.70 – 3.27) / 0.299 / 1.49 (0.69 – 3.23) / 0.314
Treatment group
Surgery + chemoradiation / Reference / Reference
Surgery + chemotherapy / 1.19 (1.02 – 1.39) / 0.027 / 1.15 (0.98 – 1.35) / 0.093
Surgery + radiation therapy / 1.18 (0.90 – 1.54) / 0.232 / 1.11 (0.82 – 1.49) / 0.500
Interaction between treatment and metformin use
Surgery + chemotherapy / - / - / 1.31 (0.83 – 2.08) / 0.251
Surgery + radiation therapy / - / - / 1.50 (0.74 – 3.06) / 0.265