Cumulative Metformin Use and Its Impact on Survival in Gastric Cancer Patients After Gastrectomy

Lee, Choong-kun; Jung, Minkyu; Jung, Inkyung; Heo, Su Jin; Jeong, Yong Hyu; An, Ji Yeong; Kim, Wook; Cheong, Jae‐Ho; Hyung, Woo Jin; Noh, Sung Hoon; Kim, Hyo Song; Rha, Sun Young; Chung, Hyun Cheol

doi:10.1097/sla.0000000000001086

Cited by 58 publications

(57 citation statements)

References 28 publications

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“…The authors suggested that the dosage of metformin should be kept low, and that treatment should be continuous. The results of the studies by Kato et al (8) and Yu et al (43) agreed with those of Lee et al (20) and Kim et al (10), who proposed that the long-term use of metformin could improve survival and significantly reduce the risk of GC.…”

Section: Selection Comparability Outcome ----------------------------supporting

confidence: 82%

“…Three studies (10,18,19) found that metformin reduced the risk of GC, whereas one study (21) showed that metformin could reduce the risk of other cancers, excluding GC. A recent clinical study (20) reported that metformin improved the survival of GC in diabetic patients subjected to gastrectomy by decreasing the recurrence, all-cause mortality, and cancer-specific mortality rates.…”

Section: Selection Comparability Outcome ----------------------------mentioning

confidence: 99%

“…The populations of the studies came from European countries (18,19) and Asian countries (10,20,21). Two included studies focused on GC, whereas the other three studies evaluated other general cancer types in addition to GC.…”

Section: Study Characteristicsmentioning

confidence: 99%

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Metformin use and its effect on gastric cancer in patients with type 2 diabetes: A systematic review of observational studies

Zhang

Gao

et al. 2017

Oncol Lett

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Abstract. Increasing evidence suggests that metformin use is associated with a decreased risk of cancer. The traditional therapies for gastric cancer (GC) are gastrectomy and chemoradiotherapy; however, these therapies may cause certain adverse effects, which affect a patient's quality of life, and the overall survival rate is low. At present, little is known about whether the use of metformin decreases the risk of GC in patients with type 2 diabetes. Therefore, in the present study, a systematic review was performed to analyze the effect of metformin on GC. A literature search was conducted in PubMed, EMBASE, and the Cochrane Library databases for articles published up to June 30th, 2016. The studies that evaluated GC patients treated with metformin and compared them with GC patients treated with other antidiabetic drugs were reviewed. Eligible studies were evaluated using the Newcastle-Ottawa Scale. Adjusted hazard ratio and 95% confidence intervals were determined to evaluate the effect of metformin on GC. From the 422 articles evaluated, 5 studies involving a total of 1,804,479 patients met the inclusion criteria and were qualitatively analyzed. The quality of all selected articles was classified as moderate. These studies reported that the long-term use of metformin was associated with a lower risk of GC compared with the lack of use of metformin or the use of other hypoglycemic drugs. In GC patients with diabetes who were subjected to gastrectomy, the cumulative use of metformin reduced the rates of disease recurrence and of all-cause and cancer-specific mortality. Despite the limited number of studies on this subject, currently available evidence indicates that metformin is associated with a decreased risk of GC and improves survival in patients with type 2 diabetes. However, more well-designed trials are required to elucidate this association.

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Section: Selection Comparability Outcome ----------------------------supporting

confidence: 82%

Section: Selection Comparability Outcome ----------------------------mentioning

confidence: 99%

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Metformin use and its effect on gastric cancer in patients with type 2 diabetes: A systematic review of observational studies

Zhang

Gao

et al. 2017

Oncol Lett

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“…A recent meta-analysis that included 5 observational studies demonstrated that adjuvant metformin therapy was significantly associated with improved, recurrence-free survival (HR, 0.63; 95% CI 0.47-0.85), overall survival (HR, 0.69; 95% CI 0.58-0.83), and cancer-specific survival (HR, 0.58; 95% CI 0.39-0.86) in CRC patients with diabetes [65]. A Korean retrospective cohort study showed that cumulative metformin use for ≥6 months was significantly associated with a decreased risk of recurrence (HR, 0.864; 95% CI 0.797-0.937), cancer-specific mortality (HR, 0.865; 95% CI 0.782-0.958), and all-cause mortality (HR, 0.870; 95% CI 0.801-0.945) in patients with gastric cancer who underwent gastrectomy [66]. However, another recent retrospective study with 43 T2DM patients failed to show significant differences in overall and disease-free survival between metformin users and non-users who underwent an esophagectomy for esophageal and esophagogastric junctional cancer after neoadjuvant chemoradiotherapy (overall survival: 43.6 vs. 21.4 months, p = 0.44; disease-free survival; 31.1 vs. 20.1 months, p = 0.31) [67].…”

Section: Metforminmentioning

confidence: 99%

Additional Benefits of Routine Drugs on Gastrointestinal Cancer: Statins, Metformin, and Proton Pump Inhibitors

Joo

Park

Chun

2017

Dig Dis

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Background: Commonly used medications including statins, metformin, and proton pump inhibitors (PPIs) effectively reduce the risk of esophageal, gastric, and colorectal cancer (CRC). Summary: A number of observational studies and meta-analyses have shown that long-term statin use significantly reduces the incidence of gastrointestinal (GI) cancer. Moreover, statin use after GI cancer diagnosis has been significantly associated with better prognosis in large-scale cohort studies. Metformin was rigorously evaluated in a population-based study and meta-analysis, and was found to have an unexpected benefit in the prevention and prolonged survival of CRC patients with type 2 diabetes mellitus. In contrast, few studies have demonstrated the chemopreventive effect of metformin for esophageal and gastric cancer. Recent observational studies have demonstrated that PPIs effectively reduce the progression of nondysplastic Barrett's esophagus into esophageal adenocarcinoma in a dose-dependent manner. However, the association between chronic PPI use and CRC or gastric cancer risk is still controversial. It was expected that these 3 routinely used medicines would show a synergistic effect with conventional systemic chemotherapy in advanced GI cancers. However, recent phase III studies failed to show significantly better outcomes. Key Messages: Further studies are needed to identify “additional” anticancer effects of these commonly used medicines.

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“…In a population survey performed in North America, Sehdev et al showed that metformin reduces the risk of colorectal cancer in patients with diabetes [74]. Furthermore, it was recently reported that an increased cumulative duration of metformin treatment decreases recurrence rate, all-cause mortality, and cancer-specific mortality in diabetic patients affected by gastric cancer [75]. In a retrospective study, Klubo-Gwiezdzinska et al found that the size of thyroid tumors was significantly smaller in patients with diabetes treated with metformin as compared with those not receiving the drug [76].…”

Section: Studies In Diabetic Patients With Cancermentioning

confidence: 96%

Expanding the therapeutic spectrum of metformin: from diabetes to cancer

Coperchini

Leporati

Rotondi

et al. 2015

J Endocrinol Invest

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Cumulative Metformin Use and Its Impact on Survival in Gastric Cancer Patients After Gastrectomy

Abstract: The increased cumulative duration of metformin use decreased the recurrence, all-cause mortality, and cancer-specific mortality rates among GC patients with diabetes who underwent gastrectomy.

Cited by 58 publications

References 28 publications

Metformin use and its effect on gastric cancer in patients with type 2 diabetes: A systematic review of observational studies

Metformin use and its effect on gastric cancer in patients with type 2 diabetes: A systematic review of observational studies

Additional Benefits of Routine Drugs on Gastrointestinal Cancer: Statins, Metformin, and Proton Pump Inhibitors

Expanding the therapeutic spectrum of metformin: from diabetes to cancer

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