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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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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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