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Peter Attia comments on Danish metformin study that does not find benefit to general population

Original study was subject to bias due to exclusion of participants who progressed to multiple therapies


Key points from article :

A 2014 retrospective study, published by Bannister et al., reported that diabetic patients on metformin monotherapy were found to have lower mortality than non-diabetic controls.

New results by Keys et al., failed to replicate the broad protective effects of metformin on lifespan.

Original study looked at diabetic patients on metformin monotherapy - with anyone progressing (as is common) to multitherapy being excluded from analysis, hence was biased toward diabetic patients who were healthiest at baseline.

Thus, the final metformin group was defined by a variable that related directly to the survival outcome of interest (a source of bias known as informative censoring).

Non-diabetic control group may have been biased toward a less health-conscious population as an absence of diagnosis will include people less likely to have regular health check-ups.

New study attempted to avoid these biases and also conducted an analysis of a same-sex twins discordant for metformin use.

Keys et al. found significantly higher mortality among diabetic patients on metformin monotherapy than among non-diabetic controls (HR = 1.97, 95% CI: 1.31 – 2.96). 

Both studies were strictly observational, meaning that they were subject to potential confounder effects.

A randomized, controlled trial is the only way to approach this question without the plague of endless confounds.

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Peter Attia

Physician at Attia Medical, PC

Topics mentioned on this page:
Metformin, Diabetes
Peter Attia comments on Danish metformin study that does not find benefit to general population