Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: A systematic review and meta-analysis
Jared M. Campbell a,b,∗, Susan M. Bellmana, Matthew D. Stephensona, Karolina Lisy. c a The Joanna Briggs Institute, The University of Adelaide, Adelaide, South Australia, Australia b Centre for Nanoscale BioPhotonics, Macquarie University, Sydney, New South Wales, Australia c Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia a r t i c l e i n f o Article history: Received 6 July 2017 Received in revised form 3 August 2017 Accepted 3 August 2017 Available online 10 August 2017 Keywords: Metformin ageing Insulin sensitizer Lifespan Longevity Geroprotection a b s t r a c t 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 Pubmed and Embase were searched along with databases of unpublished studies.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 nondiabetic 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
Jared M. Campbell a,b,∗, Susan M. Bellmana, Matthew D. Stephensona, Karolina Lisy. c a The Joanna Briggs Institute, The University of Adelaide, Adelaide, South Australia, Australia b Centre for Nanoscale BioPhotonics, Macquarie University, Sydney, New South Wales, Australia c Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia a r t i c l e i n f o Article history: Received 6 July 2017 Received in revised form 3 August 2017 Accepted 3 August 2017 Available online 10 August 2017 Keywords: Metformin ageing Insulin sensitizer Lifespan Longevity Geroprotection a b s t r a c t 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 nondiabetic 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
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