Impact of Metformin on Healthspan-Related Outcomes and Incidence of Diseases of Aging in People with Type 2 Diabetes Mellitus: A Systematic Review

Metformin use may be associated with reduced risk of all-cause mortality as well as prevent the onset of diseases of aging, namely cardiovascular diseases (CVD), cancer, and dementia. We systematically reviewed recent studies to determine whether metformin can promote healthspan in people with type 2 diabetes mellitus (T2DM). A comprehensive literature search was conducted using Medline, Embase, and Scopus for randomized controlled trials (RCTs) and cohort studies evaluating the effect of metformin on the incidence of all-cause mortality. Publications investigating metformin's effects on CVD, cancer or dementia were included. Search was restricted to English-only publications between 2016 and 2021. Full-text review, data extraction, and assessment of risk of bias using the Newcastle-Ottawa Scale were undertaken. Of 130 articles reviewed, 27 met the inclusion criteria. All 27 studies are observational cohorts, and no RCTs met the inclusion criteria, so causality cannot be inferred. No RCTs met the inclusion criteria. Five studies investigated the effects of metformin on all-cause mortality, 17 on the incidence of cancer, 3 on CVD, and 4 on dementia. Data heterogeneity precluded meta-analysis. Included studies were of high quality with NOS scores of 6-9. Metformin use in individuals with T2DM was associated with reduced risk of all-cause mortality, incidence of CVDs, and dementia. Metformin was associated with a reduced risk of prostate cancer but otherwise effects varied with cancer type and remain inconclusive.