There are several deficiencies with many of these studies, as they are mostly retrospective and do not include non-diabetic patients. In addition, authors such as Suissa5 et al have recommended cautious interpretation of many of the studies evaluating metformin and pancreatic cancer based on potential issues with time-related bias.

Based on these issues, Kordes1 and colleagues conducted a double-blind, randomized, placebo controlled study that evaluated 121 patients with confirmed metastatic disease or unresectable locally advanced pancreatic adenocarcinoma.

All patients received gemcitabine and erlotinib and then either metformin or placebo. There was no difference in overall survival or survival at 6 months. Each patient group had similar adverse events except for slightly more diarrhea and fatigue in the metformin group.

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Although this prospective study did not show a benefit of metformin in patients with pancreatic cancer, it raised several interesting issues that should be evaluated in future studies including: studying metformin use in patients with early stages of pancreatic cancer, increased use of biomarkers to identify specific patient populations that may be more susceptible to metformin’s effects, higher doses of metformin or different dosing strategies and combination of metformin with other chemotherapy regimens such as FOLFIRINOX (fluorouracil, leucovorin, irinotecan, oxaliplatin).

References

  1. Kordes S, Pollack MN, Zwindermann AH, et al. Metformin in patients with advanced pancreatic cancer: a double-blind, randomised, placebo-controlled phase 2 trial. Lancet Oncol. 2015;16(7):839-847.
  2. Sadeghi N, Abbruzzese JL, Yeung SC, et al. Metformin use is associated with better survival of diabetic patients with pancreatic cancer. Clin Cancer Res. 2012;18(10):2905-2912.
  3. Wang Z, Lai ST, Xie L, et al. Metformin is associated with reduced risk of pancreatic cancer in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetes Res Clin Pract. 2014;106(1):19-26.
  4. Tsilidis KK, Capothanassi D, Allen NE, et al. Metformin does not affect cancer risk: a cohort study in the U.K. Clinical Practice Research Datalink analyzed like an intention-to-treat trial. Diabetes Care. 2014;37:2522-2532.
  5. Suissa S, Azoulay L. Metformin and the risk of cancer: time-related biases in observational studies. Diabetes Care. 2012;35(12):2665-2673.