Differential effects of metformin on age related comorbidities in older men with type 2 diabetes
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Aims To identify distinct temporal likelihoods of age-related comorbidity (ARC) diagnoses: cardiovascular diseases (CVD), cancer, depression, dementia, and frailty-related diseases (FRD) in older men with type 2 diabetes (T2D) but ARC naïve initially, and assess the heterogeneous effects of metformin on ARCs and mortality.Methods We identified a clinical cohort of male veterans in the United States who were ≥65years old with T2D and free from ARCs during 2002-2003. ARC diagnoses during 2004-2012 were analyzed using latent class modeling adjusted for confounders.Results The cohort consisted of 41,204 T2D men with age 74.6±5.8years, HbA1c 6.5±0.97%, and 8393 (20.4%) metformin users. Four ARC classes were identified. 'Healthy Class' (53.6%): metformin reduced likelihoods of all ARCs (from 0.14% in dementia to 6.1% in CVD). 'High Cancer Risk Class' (11.6%): metformin reduced likelihoods of CVD (13.3%), cancer (45.5%), depression (5.0%), and FRD (13.7%). 'High CVD Risk Class' (17.4%): metformin reduced likelihoods of CVD (48.6%), cancer (3.2%), depression (2.8%), and FRD (6.3%). 'High Frailty Risk Class' (17.2%): metformin reduced likelihoods of CVD (18.8%), cancer (3.9%), dementia (3.8%), depression (15.6%), and FRD (23.8%).Conclusions Metformin slowed ARC development in old men with T2D, and these effects varied by ARC phenotype.
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In a large observational study of US veterans with type 2 diabetes, metformin reduced the risk of multiple age-related diseases, including cardiovascular diseases, cancer, depression, and frailty-related diseases.
“treatment with metformin reduced the risk of multiple age-related diseases, including CVDs, cancer, depression, and frailty-related diseases”
From Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty (2018) · cites this paper as [254]
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- Authors
- Wang, C.-P., Lorenzo, C., Habib, S. L., Jo, B., & Espinoza, S. E.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Stanford Medicine (US)
- Corresponding author
- Wang, Chen-Pin
- Venue
- Journal of Diabetes and its Complications
- Publisher
- Elsevier BV
- Published
- 2017-04
- Volume
- 31
- Issue
- 4
- Pages
- 679-686
- ISSN
- 0891-6632 (ISSN-L)
- 1056-8727
- PMC
- PMC5654524
- OpenAlex
- W2582066920
- Cited by
- 134
- References
- 50
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 10 · 2023: 16 · 2022: 23 · 2021: 16 · 2020: 18 · 2019: 14 · 2018: 12 · 2017: 3
- FWCI
- 5.22
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Diabetes and its Complications (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R21CA161180)
- National Institute on Aging (P30AG04427)
- National Institute on Drug Abuse (R01DA31698)
- South Texas Veterans Health Care System, San Antonio, Texas
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Epidemiology › Chronic Disease Management Strategies
- Keywords
- metformin, type 2 diabetes, older men, age-related comorbidities, cardiovascular disease, cancer, depression, dementia, frailty, mortality, veterans, treatment effect heterogeneity, latent class analysis
- MeSH terms
- Aged, Aged, 80 and over, Aging, Cardiovascular Diseases, Dementia, Depression, Diabetes Mellitus, Type 2, Drug Resistance, Humans, Hypoglycemic Agents, Longitudinal Studies, Male, Metformin, Mortality, Neoplasms, Risk, United States, United States Department of Veterans Affairs, Cohort Studies, Comorbidity, Prevalence, Frail Elderly, Electronic Health Records, Veterans Health
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