The influence of glucose-lowering therapies on cancer risk in type 2 diabetes |
| |
Authors: | C J Currie C D Poole E A M Gale |
| |
Affiliation: | (1) School of Medicine, Cardiff University, The Pharma Research Centre, Cardiff MediCentre, Cardiff, CF14 4UJ, UK;(2) Department of Epidemiology, Pharmatelligence, Cardiff, UK;(3) Diabetes and Metabolism, School of Medicine, Bristol University, Bristol, UK |
| |
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. |
| |
Keywords: | Cancer Insulin Insulin analogues Metformin Sulfonylureas Survival Type 2 diabetes |
本文献已被 SpringerLink 等数据库收录! |
|