The DOI matches its Crossref record; 49 of the 50 references it cites were found in a registry or an index.
Differential effects of metformin on age related comorbidities in older men with type 2 diabetes
Open accessAbstract
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 our case, the factors after 5 years of treatment are 0.52 for dementia, 0.33 for cardiovascular diseases, 0.32 for cancer, 0.29 for depression and 0.58 for frailty-related diseases.”
From The economic value of targeting aging (2021) · cites this paper as [28]
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“Based on ref. 28, metformin has a sizable effect on LE. For the case in which treatment starts at age 75, LE at birth rises by 2.9 years, at 20 years rises by 3.0 years, at 40 years rises by 3.0 years, at 60 years rises by 3.3 years, and at 80 years rises by 4.3 years. The additions to remaining HLE vary from 1.7 to 2.5 years.”
From The economic value of targeting aging (2021) · cites this paper as [28]
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“As ref. 28 only includes men over the age of 65 with diabetes, the factors may not accurately capture the impact of metformin on women, individuals who do not have diabetes, or those aged under 65.”
From The economic value of targeting aging (2021) · cites this paper as [28]
In the citing paper
“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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Charlson, M. E., Pompei, P., Ales, K. L., & MacKenzie, C. R. (1987) · Journal of Chronic Diseases · doi:10.1016/0021-9681(87)90171-8 · Cited by 49,742
Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes
Zinman, B., Wanner, C., Lachin, J. M., Fitchett, D., Bluhmki, E., Hantel, S., Mattheus, M., Devins, T., Johansen, O. E., Woerle, H. J., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1504720 · Cited by 12,315 · cited 1×
“…and mortality prevention requires further investigation (for example, empagliflozin has shown potential CVD prevention benefit in adults with T2D (Zinman et al., 2015)), this study provides important data for designing prospective studies aimed at examining the pleiotropic effects of metformin…”
BackgroundPrediction of coronary heart disease using risk factor categories
Wilson, P. W. F., D’Agostino, R. B., Levy, D., Belanger, A. M., Silbershatz, H., & Kannel, W. B. (1998) · Circulation · doi:10.1161/01.cir.97.18.1837 · Cited by 9,581
Cardiovascular Morbidity and Mortality Associated With the Metabolic Syndrome
Isomaa, B., Almgren, P., Tuomi, T., Forsén, B., Lahti, K., Nissén, M., Taskinen, M.-R., & Groop, L. (2001) · Diabetes Care · doi:10.2337/diacare.24.4.683 · Cited by 4,760
Prevalence, Expenditures, and Complications of Multiple Chronic Conditions in the Elderly
Wolff, J. L., Starfield, B. H., & Anderson, G. F. (2002) · Archives of Internal Medicine · doi:10.1001/archinte.162.20.2269 · Cited by 2,237
The influence of glucose-lowering therapies on cancer risk in type 2 diabetes
Currie, C. J., Poole, C. D., & Gale, E. A. M. (2009) · Diabetologia · doi:10.1007/s00125-009-1440-6 · Cited by 1,124
Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells
Zakikhani, M., Dowling, R., Fantus, I. G., Sonenberg, N., & Pollak, M. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-1500 · Cited by 1,048
Haroon, E., Raison, C. L., & Miller, A. H. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2011.205 · Cited by 1,000
Cited by
Sorted by citations
Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty
Ferrucci, L., & Fabbri, E. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0064-2 · Cited by 3,690
The quest to slow ageing through drug discovery
Partridge, L., Fuentealba, M., & Kennedy, B. K. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0067-7 · Cited by 468
Campbell, J. M., Bellman, S. M., Stephenson, M. D., & Lisy., K. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.08.003 · Cited by 455
Han, Y., Xie, H., Liu, Y., Gao, P., Yang, X., & Shen, Z. (2019) · Cardiovascular Diabetology · doi:10.1186/s12933-019-0900-7 · Cited by 337
The Therapeutic Potential of Metformin in Neurodegenerative Diseases
Rotermund, C., Machetanz, G., & Fitzgerald, J. C. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00400 · Cited by 316
Metadata
- 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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