Evidence mapPaperPMID 42399205Full record

ArticlePharmacoepidemiology and drug safety2026

Effectiveness of Metformin in Preventing Colorectal Cancer Among Japanese Patients With Type 2 Diabetes: A Target Trial Emulation.

Shunsuke Hiroki, Toshiki Fukasawa, Munenori Honda, Koji Kawakami

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Article in Pharmacoepidemiology and drug safety, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Shunsuke HirokiDepartment of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan.ORCID https://orcid.org/0009-0005-8915-7438
Toshiki FukasawaDepartment of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan.ORCID https://orcid.org/0000-0001-7147-0737
Munenori HondaDepartment of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan.ORCID https://orcid.org/0000-0001-7309-5627
Koji KawakamiDepartment of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan.ORCID https://orcid.org/0000-0002-7477-4071

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeObservational studies have repeatedly reported lower cancer incidence among metformin users than nonusers, but findings are inconsistent and often affected by issues such as immortal time, unclear comparators, and use of total cancer as a composite outcome, which precludes adequate adjustment for site-specific confounding. These limitations can be mitigated by explicitly emulating a target trial with a suitable active comparator.

methodsWe emulated a target trial using a Japanese claims database (April 2014-March 2024) to assess whether metformin reduces colorectal cancer (CRC) risk compared with dipeptidyl peptidase-4 inhibitors (DPP-4is) in patients with type 2 diabetes. DPP-4is served as an active comparator because they are widely used as first-line alternatives in Japan and have no clear evidence of affecting CRC risk. We estimated the observational analogue of the per-protocol effect using pooled logistic regression with inverse probability weighting to adjust for baseline and time-varying confounders.

resultsAmong 26 273 metformin users and 108 299 DPP-4i users, the 5-year risk of CRC was 1.55% (95% confidence interval, 1.16 to 2.04) versus 1.26% (1.13 to 1.41), yielding a risk difference of 0.29% (-0.12 to 0.79) and a risk ratio of 1.23 (0.91 to 1.66).

conclusionsMetformin use did not reduce the 5-year risk of CRC compared with DPP-4is. This finding is consistent with meta-analyses of randomized trials and contrasts with earlier observational reports of substantial benefit, which were likely inflated by methodological flaws. Explicitly emulating a target trial minimized design-related biases and provided estimates that support causal interpretation.

Indexed as

Colorectal NeoplasmsDiabetes Mellitus, Type 2Hypoglycemic AgentsMetforminAgedDatabases, FactualDipeptidyl-Peptidase IV InhibitorsEast Asian PeopleFemaleHumansIncidenceJapanMaleMiddle AgedDipeptidyl-Peptidase IV InhibitorsHypoglycemic AgentsMetformincancerimmortal timemetforminobservational studiestarget trial emulation

Identifiers

PMID42399205
PMCPMC13355942

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.