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Ageing Res Rev. 2017 Nov;40:31-44. doi: 10.1016/j.arr.2017.08.003. Epub 2017 Aug 10.

Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: A systematic review and meta-analysis.

Author information

1
The Joanna Briggs Institute, The University of Adelaide, Adelaide, South Australia, Australia; Centre for Nanoscale BioPhotonics, Macquarie University, Sydney, New South Wales, Australia. Electronic address: Jared.campbell@mq.edu.au.
2
The Joanna Briggs Institute, The University of Adelaide, Adelaide, South Australia, Australia.
3
Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Abstract

This systematic review investigated whether the insulin sensitiser metformin has a geroprotective effect in humans. Pubmed and Embase were searched along with databases of unpublished studies. Eligible research investigated the effect of metformin on all-cause mortality or diseases of ageing relative to non-diabetic populations or diabetics receiving other therapies with adjustment for disease control achieved. Overall, 260 full-texts were reviewed and 53 met the inclusion criteria. Diabetics taking metformin had significantly lower all-cause mortality than non-diabetics (hazard ratio (HR)=0.93, 95%CI 0.88-0.99), as did diabetics taking metformin compared to diabetics receiving non-metformin therapies (HR=0.72, 95%CI 0.65-0.80), insulin (HR=0.68, 95%CI 0.63-0.75) or sulphonylurea (HR=0.80, 95%CI 0.66-0.97). Metformin users also had reduced cancer compared to non-diabetics (rate ratio=0.94, 95%CI 0.92-0.97) and cardiovascular disease (CVD) compared to diabetics receiving non-metformin therapies (HR=0.76, 95%CI 0.66-0.87) or insulin (HR=0.78, 95%CI 0.73-0.83). Differences in baseline characteristics were observed which had the potential to bias findings, although statistical adjustments were made. The apparent reductions in all-cause mortality and diseases of ageing associated with metformin use suggest that metformin could be extending life and healthspans by acting as a geroprotective agent.

KEYWORDS:

Geroprotection; Insulin sensitizer; Lifespan; Longevity; Metformin; ageing

PMID:
28802803
DOI:
10.1016/j.arr.2017.08.003
[Indexed for MEDLINE]

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