The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Increased Cancer-Related Mortality for Patients With Type 2 Diabetes Who Use Sulfonylureas or Insulin
Open accessAbstract
OBJECTIVE—Numerous studies have identified an increased risk of cancer in type 2 diabetes. We explored the association between antidiabetic therapies and cancer-related mortality in patients with type 2 diabetes, postulating that agents that increase insulin levels might promote cancer. RESEARCH DESIGN AND METHODS—This was a population-based cohort study using administrative databases from Saskatchewan Health. Cancer-related mortality was compared among inception cohorts of metformin users and sulfonylurea monotherapy users. Multivariate Cox regression was used to estimate the hazard ratio (HR) of cancer-related mortality, after adjusting for age, sex, insulin use, and chronic disease score. All statistical tests were two-sided. RESULTS—We identified 10,309 new users of metformin or sulfonylureas with an average follow-up of 5.4 ± 1.9 years (means ± SD). The mean age for the cohort was 63.4 ± 13.3 years, and 55% were men. Cancer mortality over follow-up was 4.9% (162 of 3,340) for sulfonylurea monotherapy users, 3.5% (245 of 6,969) for metformin users, and 5.8% (84 of 1,443) for subjects who used insulin. After multivariate adjustment, the sulfonylurea cohort had greater cancer-related mortality compared with the metformin cohort (adjusted HR 1.3 [95% CI 1.1–1.6]; P = 0.012). Insulin use was associated with an adjusted HR of cancer-related mortality of 1.9 (95% CI 1.5–2.4; P < 0.0001). CONCLUSIONS—Patients with type 2 diabetes exposed to sulfonylureas and exogenous insulin had a significantly increased risk of cancer-related mortality compared with patients exposed to metformin. It is uncertain whether this increased risk is related to a deleterious effect of sulfonylurea and insulin or a protective effect of metformin or due to some unmeasured effect related to both choice of therapy and cancer risk.
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“The reduced risk of cancer and cancer mortality observed in these studies has been consistently in the range of 25% to 30% [135-139,145-147].”
From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [147]
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“Results of a growing number of observational human studies suggest that treatment with metformin (relative to other glucose-lowering therapies) is associated with reduced risk of cancer (89–93) or cancer mortality (94).”
From Diabetes and Cancer (2010) · cites this paper as [90]
In the citing paper
“Patients with type 2 diabetes who are prescribed metformin had a lower risk of cancer compared to patients who did not take it.”
From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [147]
In the citing paper
“Patients with type 2 diabetes exposed to sulfonylureas and exogenous insulin had a significantly increased risk of cancer-related mortality compared with patients exposed to metformin.”
From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [147]
In the citing paper
“A small number of observational studies found a higher risk of cancer or cancer death among individuals with diabetes treated with sulfonylureas compared with those treated with metformin or other diabetes medications (90–92,110).”
From Diabetes and Cancer (2010) · cites this paper as [90]
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Cites
Metformin and reduced risk of cancer in diabetic patients
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Efficacy of Metformin in Patients with Non-Insulin-Dependent Diabetes Mellitus
DeFronzo, R. A., & Goodman, A. M. (1995) · New England Journal of Medicine · doi:10.1056/nejm199508313330902 · Cited by 1,368
A chronic disease score from automated pharmacy data
Korff, M. V., Wagner, E. H., & Saunders, K. W. (1992) · Journal of Clinical Epidemiology · doi:10.1016/0895-4356(92)90016-g · Cited by 962
Giovannucci, E. L. (1995) · Cancer Causes & Control · doi:10.1007/bf00052777 · Cited by 808
Diabetes Mellitus as a Predictor of Cancer Mortality in a Large Cohort of US Adults
Coughlin, S. S., Calle, E. E., Teras, L. R., Petrelli, J. M., & Thun, M. J. (2004) · American Journal of Epidemiology · doi:10.1093/aje/kwh161 · Cited by 795
Diabetes mellitus as a risk factor for pancreatic cancer. A meta-analysis
Everhart, J. (1995) · JAMA · doi:10.1001/jama.273.20.1605 · Cited by 747
Johnson, J. A., Majumdar, S. R., Simpson, S. H., & Toth, E. L. (2002) · Diabetes Care · doi:10.2337/diacare.25.12.2244 · Cited by 421
Self-citationProspective Study of Adult Onset Diabetes Mellitus (Type 2) and Risk of Colorectal Cancer in Women
Hu, F. B., Manson, J. E., Liu, S., Hunter, D. J., Colditz, G. A., Michels, K. B., Speizer, F. E., & Giovannucci, E. L. (1999) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/91.6.542 · Cited by 420
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Guyatt, G. H., Oxman, A. D., Vist, G., Kunz, R., Brozek, J., Alonso-Coello, P., Montori, V., Akl, E. A., Djulbegovic, B., & Falck-Ytter, Y. (2011) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2010.07.017 · Cited by 2,798
Giovannucci, E., Harlan, D. M., Archer, M. C., Bergenstal, R. M., Gapstur, S. M., Habel, L. A., Pollak, M., Regensteiner, J. G., & Yee, D. (2010) · Diabetes Care · doi:10.2337/dc10-0666 · Cited by 2,366
Insulin and insulin-like growth factor signalling in neoplasia
Pollak, M. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2536 · Cited by 2,059
GRADE guidelines: 2. Framing the question and deciding on important outcomes
Guyatt, G. H., Oxman, A. D., Kunz, R., Atkins, D., Brozek, J., Vist, G., Alderson, P., Glasziou, P., Falck-Ytter, Y., & Schünemann, H. J. (2011) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2010.09.012 · Cited by 1,911
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Metadata
- Authors
- Bowker, S. L., Majumdar, S. R., Veugelers, P., & Johnson, J. A.
- Affiliations
- University of Alberta (CA)
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2006-02-01
- Volume
- 29
- Issue
- 2
- Pages
- 254-258
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2156370651
- Cited by
- 933
- References
- 37
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 28 · 2023: 32 · 2022: 26 · 2021: 25 · 2020: 33 · 2019: 37 · 2018: 33 · 2017: 45 · 2016: 43 · 2015: 52 · 2014: 55 · 2013: 96 · 2012: 93
- FWCI
- 16.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- 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 › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- type 2 diabetes, cancer mortality, sulfonylureas, insulin therapy, metformin, antidiabetic drugs, cancer risk
- MeSH terms
- Aged, Diabetes Mellitus, Type 2, Drug Therapy, Combination, Female, Follow-Up Studies, Humans, Hypoglycemic Agents, Insulin, Male, Metformin, Middle Aged, Neoplasms, Retrospective Studies, Risk Factors, Saskatchewan, Severity of Illness Index, Sulfonylurea Compounds, Cohort Studies, Comorbidity, Multivariate Analysis, Proportional Hazards Models
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