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Cited by 1,124Metabolism, Diabetes, and CancerDiabetes Treatment and ManagementDiabetes Management and Research

The influence of glucose-lowering therapies on cancer risk in type 2 diabetes

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Currie, C. J., Poole, C. D., Gale, E. A. M.·2009·Diabetologia
DOI 10.1007/s00125-009-1440-6
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Abstract

Aims/hypothesis The risk of developing a range of solid tumours is increased in type 2 diabetes, and may be influenced by glucose-lowering therapies. We examined the risk of development of solid tumours in relation to treatment with oral agents, human insulin and insulin analogues.Methods This was a retrospective cohort study of people treated in UK general practices. Those included in the analysis developed diabetes >40 years of age, and started treatment with oral agents or insulin after 2000. A total of 62,809 patients were divided into four groups according to whether they received monotherapy with metformin or sulfonylurea, combined therapy (metformin plus sulfonylurea), or insulin. Insulin users were grouped according to treatment with insulin glargine, long-acting human insulin, biphasic analogue and human biphasic insulin. The outcome measures were progression to any solid tumour, or cancer of the breast, colon, pancreas or prostate. Confounding factors were accounted for using Cox proportional hazards models.Results Metformin monotherapy carried the lowest risk of cancer. In comparison, the adjusted HR was 1.08 (95% CI 0.96-1.21) for metformin plus sulfonylurea, 1.36 (95% CI 1.19-1.54) for sulfonylurea monotherapy, and 1.42 (95% CI 1.27-1.60) for insulin-based regimens. Adding metformin to insulin reduced progression to cancer (HR 0.54, 95% CI 0.43-0.66). The risk for those on basal human insulin alone vs insulin glargine alone was 1.24 (95% CI 0.90-1.70). Compared with metformin, insulin therapy increased the risk of colorectal (HR 1.69, 95% CI 1.23-2.33) or pancreatic cancer (HR 4.63, 95% CI 2.64-8.10), but did not influence the risk of breast or prostate cancer. Sulfonylureas were associated with a similar pattern of risk as insulin.Conclusions/interpretation Those on insulin or insulin secretagogues were more likely to develop solid cancers than those on metformin, and combination with metformin abolished most of this excess risk. Metformin use was associated with lower risk of cancer of the colon or pancreas, but did not affect the risk of breast or prostate cancer. Use of insulin analogues was not associated with increased cancer risk as compared with human insulin.

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  • Treatment with metformin relative to other glucose-lowering therapies is associated with reduced risk of cancer or cancer mortality in observational human studies.

    “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 [91]

  • 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.

    “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 [91]

  • Most of these studies had very few cancer cases among users of sulfonylureas, so power was limited to examine associations with specific cancer sites.

    “However, most of these studies had very few cancer cases among users of sulfonylureas, and therefore power was limited to examine associations with specific cancer sites (91,111).”

    From Diabetes and Cancer (2010) · cites this paper as [91]

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Authors
Currie, C. J., Poole, C. D., & Gale, E. A. M.
Affiliations
  • Cardiff University (GB)
  • University of Bristol (GB)
Corresponding author
Currie, C. J.
Venue
Diabetologia
Publisher
Springer Science and Business Media LLC
Published
2009-07-02
Volume
52
Issue
9
Pages
1766-1777
ISSN
  • 0012-186X (ISSN-L)
  • 1432-0428
DOI
10.1007/s00125-009-1440-6
OpenAlex
W2169214947
Cited by
1,124
References
24
Citations by year
2026: 17 · 2025: 15 · 2024: 27 · 2023: 25 · 2022: 31 · 2021: 42 · 2020: 44 · 2019: 50 · 2018: 50 · 2017: 65 · 2016: 63 · 2015: 76 · 2014: 99 · 2013: 122 · 2012: 126
FWCI
53.20
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Diabetologia (publishedVersion)
  • PubMed (publishedVersion)
  • Explore Bristol Research (submittedVersion)
Funders
  • Eli Lilly and Company
  • GlaxoSmithKline
  • Sanofi
  • Novo Nordisk
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, glucose-lowering therapy, cancer risk, solid tumors, metformin, sulfonylureas, insulin, insulin glargine, insulin analogues, colorectal cancer, pancreatic cancer, breast cancer, prostate cancer, insulin secretagogues, drug safety, cancer risk reduction, combination therapy, general practice patients, UK Biobank
MeSH terms
Administration, Oral, Adult, Aged, Aged, 80 and over, Blood Pressure, Diabetes Mellitus, Type 2, Family Practice, Female, United Kingdom, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Insulin, Male, Metformin, Neoplasms, Retrospective Studies, Risk Factors, Cohort Studies, Disease Progression, Risk Assessment

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