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Improved Survival following Pancreatic Cancer among Patients Receiving Metformin
Marcelo Cerullo*, Faiz Gani, Joseph K. Canner, Timothy M. Pawlik
Surgery, Johns Hopkins Hospital, Baltimore, MD

Background: Preclinical evidence has demonstrated anti-tumorigenic effects of metformin, associating metformin use with improved survival and decreased recurrence following resection of endometrial and gastric cancer. The effects of metformin following pancreatic cancer remain undefined. We sought to assess the association between metformin use and survival using a large, nationally representative sample of patients undergoing surgery for pancreatic cancer.
Methods: Patients undergoing a pancreatic resection between January 01, 2010 and December 31, 2012 were identified using the Truven Health MarketScan database. Clinical data, including history of metformin use, as well as operative details and information on long-term outcomes were collected. Multivariable Cox proportional hazards regression analysis was performed to assess the effect of metformin use on overall survival (OS).
Results: A total of 3,401 patients were identified. The mean age of patients was 54.2 years (SD=9.1 years). Roughly one-half of patients were female (n=1,739, 51.2%); 49.1% (n=1,669) presented with a Charlson co-morbidity index of 3 or greater (CCI≥3) and 18.7% (n=636) had diabetes. At the time of surgery, 60.1% (n=2,044) of patients underwent a pancreaticoduodenectomy, 35.5% (n=1,207) a partial/distal pancreatectomy, while 4.4% (n=150) had a total pancreatectomy. On pathology, 1,059 (31.1%) had lymph node metastasis. Metformin use was identified in 284 patients (8.4%) and was more commonly administered among patients without locally advanced disease (6.80% vs. 9.06%, p=0.028). While OS was comparable between patients within the first year of surgery (OS at 1 year: 65.4% [95%CI 63.5%-67.3%] vs. 71.2% [95%CI 64.8%-76.6%]), patients who received metformin demonstrated an improved OS beginning at 18 months following surgery. On multivariable analysis adjusting for patient and clinicopathologic characteristics, risk factors associated with a higher risk of death included age (HR 1.03, 95%CI 1.02-1.04, p<0.001) and CCI≥3 (HR 1.64, 95%CI 1.33-2.02, p=0.02). In contrast, metformin use was independently associated with a decreased risk of mortality (HR 0.71, 95% CI: 0.58-0.88, p<0.001).
Conclusions: Metformin use was associated with an improved overall survival among patients undergoing pancreatic surgery for pancreatic cancer. Further work is necessary to better understand metformin's role in modifying cancer specific and overall health outcomes.

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