Metformin Does Not Affect Cancer Risk: A Cohort Study in the U.K. Clinical Practice Research Datalink Analyzed Like an Intention-to-Treat Trial

Tsilidis, Konstantinos K.; Capothanassi, Despoina; Allen, Naomi E.; Rizos, Evangelos C.; López, David S.; Veldhoven, Karin van; Sacerdote, Carlotta; Ashby, Deborah; Víneis, Paolo; Tzoulaki, Ioanna; Ioannidis, John P. A.

doi:10.2337/dc14-0584

Cited by 157 publications

(153 citation statements)

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“…association between metformin and colon cancer (RR¼0.80, 95% CI: 0.64-1.00) by including 12 included studies without three new studies in 2014 (Cardel et al 2014;Tsilidis et al 2014;Xu et al 2014), which were included in our study. These results imply the potential effects of metformin against the occurrence of colon cancer in T2DM patients.…”

Section: Discussionmentioning

confidence: 99%

“…Table 1 shows that eight cohort studies (Oliveria et al 2008;Currie et al 2009;Libby et al 2009;Lee et al 2011;Hsieh et al 2012;Ruiter et al 2012;Tsilidis et al 2014;Xu et al 2014) including 175,432 cases and 126,967 controls, and three case-control studies (Yang et al 2004;Bodmer et al 2012;Cardel et al 2014) including 3133 cases and 15,774 controls were retrieved in the meta-analysis. Two studies were based on American (Oliveria et al 2008;Xu et al 2014), seven studies were based on European (Yang et al 2004;Currie et al 2009;Libby et al 2009;Bodmer et al 2012;Ruiter et al 2012;Cardel et al 2014;Tsilidis et al 2014), and two studies were based on Chinese (Taiwan) (Lee et al 2011;Hsieh et al 2012). All the studies were published from 2004 to 2014.…”

Section: Publication Selectionmentioning

confidence: 99%

“…The remaining 21 articles were all full-reviewed. Bodmer et al 2012;Hsieh et al 2012;Ruiter et al 2012;Cardel et al 2014;Tsilidis et al 2014;Xu et al 2014) were enrolled in the meta-analysis. No study was included after hand-checking.…”

Section: Publication Selectionmentioning

confidence: 99%

“…Several epidemiological studies reported significantly decreased CRC incidence among T2DM treated with metformin (Oliveria et al 2008;Currie et al 2009;Libby et al 2009;Lee et al 2011;Hsieh et al 2012;Ruiter et al 2012). However, other studies did not detect the relationship between metformin treatment and CRC risk among diabetes (Yang et al 2004;Bodmer et al 2012;Cardel et al 2014;Tsilidis et al 2014;Xu et al 2014). Several meta-analyses were conducted to evaluate the relationship, while the tissue still remains controversial (Decensi et al 2010;Zhang et al 2011;Noto et al 2012;Soranna et al 2012;Gandini et al 2014).…”

Section: Introductionmentioning

confidence: 99%

“…Gandini et al (2014) performed a new meta-analysis, which shows that metformin may reduce cancer incidence and mortality in patients with diabetes, including the colon cancer. Thereafter, several further studies were conducted to explore the relationship between metformin therapy and CRC risk among T2DM (Tsilidis et al 2014;Xu et al 2014). Accordingly, we performed the meta-analysis through enrolling the studies focusing on the tissue associated with the relationship exposition.…”

Section: Introductionmentioning

confidence: 99%

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Reduced colorectal cancer incidence in type 2 diabetic patients treated with metformin: a meta-analysis

Nie

Zhu

2016

Pharmaceutical Biology

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Context: Diabetic patients have a higher risk of colorectal cancer (CRC). The role of metformin in CRC incidence among type 2 diabetes mellitus (T2DM) remains controversial. Objective: A meta-analysis was performed to evaluate the role of metformin treatment in the occurrence of CRC among T2DM patients. Methods: Search was performed throughout PubMed, Embase, Springer databases up to November 2014. The search terms were (biguanides or metformin) and (bowel or colon or rectal or colorectal) and (cancer or neoplasm or neoplasia). Relative risk (RR) and 95% confidence interval (CI) was pooled using randomeffects model or fixed-effect model basing on heterogeneity, which was calculated basing on Q statistics and v 2 test. In addition, subgroup analyses were performed according to region, study design and control treatment. Finally, publication bias was evaluated using Egger's regression test and trim and fill analysis. Results: A total of 11 studies, including eight cohort studies and three case-control studies, were enrolled in the meta-analysis. Obvious heterogeneity was noted, and a 25% lower CRC incidence was found among diabetic patients treated with metformin (pooled RR¼0.75, 95% CI: 0.66-0.86), using the random-effects model. Subgroup analyses showed that CRC incidence significantly reduced among T2DM in different regions, non-metformin treatment and cohort studies. Evidence supported significant publication for studies investigating from Egger's regression test. Conversely, no missing data were found using trim and fill analysis. Conclusion: In conclusion, the meta-analysis suggests metformin may reduce CRC incidence among diabetics, which is useful medical information for clinicians. ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 99%

Section: Publication Selectionmentioning

confidence: 99%

Section: Publication Selectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Reduced colorectal cancer incidence in type 2 diabetic patients treated with metformin: a meta-analysis

Nie

Zhu

2016

Pharmaceutical Biology

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Reporting of Observational Studies Explicitly Aiming to Emulate Randomized Trials

Hansford,

Cashin,

Jones

et al. 2023

JAMA Netw Open

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ImportanceObservational (nonexperimental) studies that aim to emulate a randomized trial (ie, the target trial) are increasingly informing medical and policy decision-making, but it is unclear how these studies are reported in the literature. Consistent reporting is essential for quality appraisal, evidence synthesis, and translation of evidence to policy and practice.ObjectiveTo assess the reporting of observational studies that explicitly aimed to emulate a target trial.Evidence ReviewWe searched Medline, Embase, PsycINFO, and Web of Science for observational studies published between March 2012 and October 2022 that explicitly aimed to emulate a target trial of a health or medical intervention. Two reviewers double-screened and -extracted data on study characteristics, key predefined components of the target trial protocol and its emulation (eligibility criteria, treatment strategies, treatment assignment, outcome[s], follow-up, causal contrast[s], and analysis plan), and other items related to the target trial emulation.FindingsA total of 200 studies that explicitly aimed to emulate a target trial were included. These studies included 26 subfields of medicine, and 168 (84%) were published from January 2020 to October 2022. The aim to emulate a target trial was explicit in 70 study titles (35%). Forty-three studies (22%) reported use of a published reporting guideline (eg, Strengthening the Reporting of Observational Studies in Epidemiology). Eighty-five studies (43%) did not describe all key items of how the target trial was emulated and 113 (57%) did not describe the protocol of the target trial and its emulation.Conclusion and RelevanceIn this systematic review of 200 studies that explicitly aimed to emulate a target trial, reporting of how the target trial was emulated was inconsistent. A reporting guideline for studies explicitly aiming to emulate a target trial may improve the reporting of the target trial protocols and other aspects of these emulation attempts.

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Aspirin, metformin, and statin use on the risk of gastric cancer: A nationwide population‐based cohort study in Korea with systematic review and meta‐analysis

et al. 2021

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Background/Aims Although several chemopreventive drugs against gastric cancer have been proposed, their effects have not been fully evaluated. We examined the impacts of aspirin, metformin, and statin use on gastric cancer development in a population‐based cohort in Korea. Methods We analyzed the association between potential chemopreventive drugs—aspirin, metformin, and statin—and gastric cancer through the Observational Medical Outcomes Partnership Common Data Model‐based Korean nationwide cohort. Use of aspirin, metformin, and statin was defined by ≥365 days of prescriptions for each drug in the general population. To summarize the current evidence, we further performed a systematic review and meta‐analysis of the impact of aspirin, metformin, and statin on gastric cancer development. Results After propensity score matching, 31,839, 6764, and 10,251 subjects were observed for medians of 4.7, 4.2, and 4.2 years for aspirin, metformin, and statin analysis, respectively. Use of aspirin or statin was associated with lower risks of gastric cancer compared to their non‐use, respectively (hazard ratio [HR] [95% confidence interval [CI]]: aspirin, 0.72 [0.60–0.85], p < 0.01; statin, 0.67 [0.49–0.92], p = 0.01). However, no association was observed between metformin use and gastric cancer development (HR [95% CI]: 0.85 [0.59–1.23], p = 0.40). A subgroup of subjects with diabetes mellitus showed a lower risk of gastric cancer development with statin use. The meta‐analysis showed the highest effect size of gastric cancer development for statin, followed by aspirin and metformin. Conclusions Statin and aspirin use were associated with significantly reduced risks of gastric cancer development, while the use of metformin was not associated with the gastric cancer risk. The protective effect of statin against gastric cancer was also significant in patients with diabetes mellitus.

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Metformin Does Not Affect Cancer Risk: A Cohort Study in the U.K. Clinical Practice Research Datalink Analyzed Like an Intention-to-Treat Trial

Cited by 157 publications

References 30 publications

Reduced colorectal cancer incidence in type 2 diabetic patients treated with metformin: a meta-analysis

Reduced colorectal cancer incidence in type 2 diabetic patients treated with metformin: a meta-analysis

Reporting of Observational Studies Explicitly Aiming to Emulate Randomized Trials

Aspirin, metformin, and statin use on the risk of gastric cancer: A nationwide population‐based cohort study in Korea with systematic review and meta‐analysis

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