Metformin and pancreatic cancer: Is there a role?

Souza, André De; Khawaja, Khadija Irfan; Masud, Faisal; Saif, Muhammad Wasif

doi:10.1007/s00280-015-2948-8

Cited by 45 publications

(36 citation statements)

References 64 publications

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“…As the potential role of anti-diabetic drugs (metformin and insulin) in influencing pancreatic carcinogenesis has been reported (De Souza et al 2016), we also specifically investigated the role of such drugs in our multinational cohort. Although the prevalent use of insulin alone was more frequent among cases than in controls (4.1% vs 1.6%), this difference was not significant as the study was underpowered to assess it.…”

Section: Discussionmentioning

confidence: 99%

Risk and protective factors for the occurrence of sporadic pancreatic endocrine neoplasms

Valente¹,

Hayes²,

Haugvik³

et al. 2017

Endocrine-Related Cancer

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Pancreatic neuroendocrine neoplasms (PNENs) represent 10% of all pancreatic tumors by prevalence. Their incidence has reportedly increased over recent decades in parallel with that of pancreatic adenocarcinoma. PNENs are relatively rare, and of the few institutions that have published potential risk factors, findings have been heterogeneous. Our objective was to investigate the association between potential risk and protective factors for the occurrence of sporadic PNENs across a European population from several institutions. A multinational European case-control study was conducted to examine the association of selected environmental, family and medical exposure factors using a standardized questionnaire in face-to-face interviews. A ratio of 1:3 cases to controls were sex and age matched at each study site. Adjusted univariate and multivariate logistic regression analysis were performed for statistically significant factors. The following results were obtained: In 201 cases and 603 controls, non-recent onset diabetes (OR 2.09, CI 1.27-3.46) was associated with an increased occurrence of PNENs. The prevalence of non-recent onset diabetes was higher both in cases with metastatic disease (TNM stage III-IV) or advanced grade (G3) at the time of diagnosis. The use of metformin in combination with insulin was also associated with a more aggressive phenotype. Drinking coffee was more frequent in cases with localized disease at diagnosis. Our study concluded that non-recent onset diabetes was associated with an increased occurrence of PNENs and the combination of metformin and insulin was consistent with a more aggressive PNEN phenotype. In contrast to previous studies, smoking, alcohol and first-degree family history of cancer were not associated with PNEN occurrence.

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Section: Discussionmentioning

confidence: 99%

Risk and protective factors for the occurrence of sporadic pancreatic endocrine neoplasms

Valente¹,

Hayes²,

Haugvik³

et al. 2017

Endocrine-Related Cancer

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“…There is growing consensus that diabetes is a potential cause of pancreatic cancer [10]. Currently, chemotherapy serves as a main supplementation when necessary subsequent to surgery for pancreatic cancer patients at an early stage as well as the primary therapeutic regimen for advanced pancreatic cancer, achieving remarkable benefit, however with evident increase in deleterious effects in relation to the nonspecific damage at the meantime [8].…”

Section: Discussionmentioning

confidence: 99%

“…Accumulating evidences suggested a preventive role of the well-known anti-diabetic drug metformin accompanied with chemotherapy and radiotherapy in the malignance of cancer cell by inhibiting cell division, promoting apoptosis and autophagy, down-regulating circulating insulin, activating the immune system and crippling irradiation-resistance [8][9][10]. The preventive role of metformin was shown in multiple cancer types, including pancreatic, colorectal, prostate, and hepatocellular carcinoma, resulting in decreased cancer incidence and mortality [11,12].…”

Section: Introductionmentioning

confidence: 99%

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Survival Benefit of Metformin Adjuvant Treatment For Pancreatic Cancer Patients: a Systematic Review and Meta-Analysis

Wan

Sun

et al. 2018

Cell Physiol Biochem

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Background/Aims: Previous studies on the effect of metformin therapy on survival of pancreatic cancer patients obtained inconsistent findings. To reevaluate the prognostic value of metformin adjuvant treatment, a meta-analysis was carried out. Methods: Relevant articles addressing the association between metformin use and pancreatic cancer survival were electronically searched to identify eligible studies. Pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated to assess the strength of the association. Results: Totally, seventeen studies involving 36791 participants were included. Overall, metformin use was found to be significantly associated with a favorable OS (HR=0.88, 95% CI=0.80-0.97). Subgroup analyses by ethnicity showed a significantly reduced risk of death for metformin users compared with non-users in Asians (HR=0.74, 95% CI=0.58-0.94) but nonsignificant in Caucasians. When stratified by clinical stage, a remarkable reduction of mortality risk in patients at stage I-II treated with metformin (HR=0.76, 95% CI=0.68-0.86) was found as well as the group at stage I-IV (HR=0.88, 95% CI=0.79-0.99), but not in patients at stage III-IV. In the stratification analyses based on treatment strategy, metformin therapy was found to be associated with a better clinical outcome in patients receiving surgery or comprehensive therapy (HR=0.73, 95% CI=0.62-0.87; HR=0.88, 95% CI=0.79-0.97) but not chemotherapy. However, the overall analysis failed to show a significant association between metformin use and DFS (HR=1.54, 95% CI=0.94 -2.50) with only 2 studies enrolled. Conclusion: The current study has evidenced a significant association of metformin adjuvant treatment with the survival benefit for pancreatic cancer patients, suggesting a potentially available option for the treatment. Further investigation is needed.

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“…For example, studies have shown a survival benefit in diabetic patients with pancreatic cancer that have been treated with metformin compared with patients treated with insulin or sulfonylureas. [32,33] However, there is limitation on applying registry data to elucidate the association between medication history and the occurrence of pancreatic cancer. Further study should be conducted to specifically deal with this interesting topic.…”

Section: Discussionmentioning

confidence: 99%