The effect of metformin on esophageal cancer risk in patients with type 2 diabetes mellitus: a systematic review and meta‑analysis

Wu, Huadong; Zhang, J.-J.; Zhou, Baojun

doi:10.1007/s12094-020-02415-6

Cited by 10 publications

(7 citation statements)

References 43 publications

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“…A meta-analysis of 21 studies showed that metformin might be beneficial for survival in patients with pancreatic cancer and diabetes ( 99 ). Wu et al found that metformin had no effect on the overall esophageal cancer risk, but it may reduce esophageal cancer risk in T2D Asian patients ( 100 ). Du et al's research reported in diabetics of colorectal cancer patients that taking metformin can improve overall survival and cancer specific survival, especially the overall survival of patients with stage II and III ( 101 ).…”

Section: Discussionmentioning

confidence: 99%

SGLT-2i and Risk of Malignancy in Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials

Shi

et al. 2021

Front. Public Health

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Background: Currently, the association between sodium-glucose cotransporter 2 inhibitor (SGLT-2i) and malignancy risk has yet to be fully elucidated. This meta-analysis aimed to determine the relationship between SGLT-2i and malignancy risk in type 2 diabetes (T2D) patients.Methods: We searched PubMed, ScienceDirect, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science to identify randomized controlled trials (RCTs) published up to August 2020 related to T2D patients treated with SGLT-2i vs. placebo or other hypoglycemic agents. The meta-analysis's primary outcome was malignancies' incidence, and the results were evaluated using risk ratio (RR) and 95% confidence interval (CI).Results: We reviewed 76 articles (77 RCTs), comprising 45,162 and 43,811 patients in SGLT-2i and control groups, respectively. Compared with the control group, SGLT-2i had no significant association with augmented overall malignancy risk in T2D patients (RR = 1.05, 95% CI = 0.97–1.14, P = 0.20), but ertugliflozin may upsurge the risk (RR = 1.80, 95% CI = 1.02–3.17, P = 0.04). Compared with active hypoglycemic agents, dapagliflozin may increase (RR = 2.71, 95% CI = 1.46–6.43, P = 0.02) and empagliflozin may decrease (RR = 0.67, 95% CI = 0.45–0.98, P = 0.04) the malignancy risk. Compared with placebo, empagliflozin may exhibit risk increase (RR = 1.25, 95% CI = 1.05–1.49, P = 0.01), primarily in digestive system (RR = 1.48, 95% CI = 0.99–2.21, P = 0.05).Conclusions: Our results proposed that in diverse comparisons, ertugliflozin and dapagliflozin seemed to increase the malignancy risk in T2D patients. Empagliflozin may cause malignancy risk reduction compared with active hypoglycemic agents but increase overall risk primarily in the digestive system compared with placebo. In short, the relationship between SGLT-2i and malignancy in T2D patients remains unclear.

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Section: Discussionmentioning

confidence: 99%

SGLT-2i and Risk of Malignancy in Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials

Shi

et al. 2021

Front. Public Health

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“…Metformin may potentially enhance the release of 5'adenosine monophosphate (AMP-) activated protein kinase (AMPK) at a low level of insulin in the blood, thus impeding the production and elevation of cancerous cellular proteins [32]. Nevertheless, recent investigations on the in uence of metformin in decreasing the occurrence of oesophageal cancer have contradictory ndings [33,34]. More large-scale research is necessary to elucidate its signi cance in reducing the risk of oesophageal cancer among individuals with T2DM.…”

Section: Discussionmentioning

confidence: 99%

Association Between Glycemic Traits and Oesophageal Cancer: a Multivariable Mendelian Randomization Study

Chen,

Zeng,

et al. 2023

Preprint

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Background Observational studies indicate a potential link between increased blood glucose levels and the development of oesophageal cancer. However, the causal relationship between glycemic traits and oesophageal cancer has not been clarified yet. The aim of this research was to examine if there is a genetic link between glycemic characteristics and oesophageal cancer through the use of Mendelian randomization analysis. Methods We conducted a TSMR analysis and MVMR using publicly available GWAS data on the European population. The primary analysis utilized the IVW method, which was subsequently validated through comprehensive complementary and sensitivity analyses. Results IVW analysis revealed a substantial correlation (OR = 1.612, P = 0.0228) between type 2 diabetes (T2DM) and oesophageal cancer. After accounting for body mass index (BMI), this association remained to be statistically significant in multivariate MR analyses (OR = 1.662, P = 0.0416). There was only a small amount of evidence indicating a possible link between oesophageal cancer and other glycemic traits after excluding the outliers. Conclusions Our study further supports the evidence that European individuals with T2DM are at an increased risk of developing oesophageal cancer. It implies that pharmacological or lifestyle treatments for individuals with T2DM could potentially be advantageous in the prevention of oesophageal tumor development.

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“…Data from two recent meta-analyses present contradictory findings [ 38 , 39 ]. Chen et al examined the association between metformin use and the risk of EC.…”

Section: Metformin In Esophageal Cancer: Exploring Its Clinical Signi...mentioning

confidence: 99%

“…They indicated that metformin did not significantly reduce the risk of EC in patients with T2DM (HR 0.88, 95% CI 0.60–1.28, p > 0.05). However, subgroup analyses by geographic location revealed a significant reduction in esophageal cancer risk associated with metformin in Asian patients with T2DM (HR 0.59, 95% CI 0.39–0.91, p = 0.02), with no heterogeneity between studies [ 39 ]. In conclusion, while metformin did not show a notable reduction in EC risk in T2DM patients overall, a significant risk reduction was observed in Asian populations, although further clarification is needed.…”

Section: Metformin In Esophageal Cancer: Exploring Its Clinical Signi...mentioning

confidence: 99%

Metformin in Esophageal Carcinoma: Exploring Molecular Mechanisms and Therapeutic Insights

Papadakos,

Argyrou,

Lekakis

et al. 2024

IJMS

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Esophageal cancer (EC) remains a formidable malignancy with limited treatment options and high mortality rates, necessitating the exploration of innovative therapeutic avenues. Through a systematic analysis of a multitude of studies, we synthesize the diverse findings related to metformin’s influence on EC. This review comprehensively elucidates the intricate metabolic pathways and molecular mechanisms through which metformin may exert its anti-cancer effects. Key focus areas include its impact on insulin signaling, AMP-activated protein kinase (AMPK) activation, and the mTOR pathway, which collectively contribute to its role in mitigating esophageal cancer progression. This review critically examines the body of clinical and preclinical evidence surrounding the potential role of metformin, a widely prescribed anti-diabetic medication, in EC management. Our examination extends to the modulation of inflammation, oxidative stress and angiogenesis, revealing metformin’s potential as a metabolic intervention in esophageal cancer pathogenesis. By consolidating epidemiological and clinical data, we assess the evidence that supports metformin’s candidacy as an adjuvant therapy for esophageal cancer. By summarizing clinical and preclinical findings, our review aims to enhance our understanding of metformin’s role in EC management, potentially improving patient care and outcomes.

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The effect of metformin on esophageal cancer risk in patients with type 2 diabetes mellitus: a systematic review and meta‑analysis

Cited by 10 publications

References 43 publications

SGLT-2i and Risk of Malignancy in Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials

SGLT-2i and Risk of Malignancy in Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials

Association Between Glycemic Traits and Oesophageal Cancer: a Multivariable Mendelian Randomization Study

Metformin in Esophageal Carcinoma: Exploring Molecular Mechanisms and Therapeutic Insights

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