This article is a collaboration between MedPage Today® and:
Insulin sensitizing agents may carry a lower risk of cancer for women with type 2 diabetes than insulin secretagogues, researchers found.
In a retrospective review of a large data set, insulin sensitizers such as thiazolidinediones (TZDs) and metformin were associated with a 21% decreased cancer risk for women compared with insulin secretagogues such as sulfonylureas, Sangeeta Kashyap, MD, of Cleveland Clinic, and colleagues reported online in Diabetes, Obesity, & Metabolism.
TZDs in particular carried a much lower risk of cancer in women with diabetes compared with sulfonylureas, they found.
The findings "contribute to a growing body of evidence that drugs increasing endogenous insulin levels may promote carcinogenesis," they wrote, adding that it's "important to consider the impact a drug has on fueling cancer growth" when prescribing drugs for diabetes.
The study, however, didn't look at incretin therapies, such as GLP-1 agonists and DPP-4 inhibitors, that have been increasingly prescribed in more recent years.
Insulin sensitizers lower blood sugar by increasing sensitivity to insulin in muscle, fat, and in the liver, while secretagogues get the beta cells to produce more insulin, increasing endogenous levels of the hormone and potentially activating insulin-like growth factor-1 pathways (IGF-1) -- a potential risk for cancer.
For their study, Kashyap and colleagues looked at data from the Cleveland Clinic Diabetes Registry on 25,613 patients and compared that with histology-based tumor registry data on 48,051 cancer occurrences from 1998 to 2006.
They identified more than 890 incident cancer cases, with the most common cancers being prostate and breast, accounting for more than 25% of total cancers.
Overall, they found that insulin sensitizers were associated with a 21% lower risk of cancer compared with insulin secretagogues -- but only in women (HR 0.79, 95% CI 0.64 to 0.98).
Specifically, thiazolidinediones were linked to a 32% lower cancer risk compared with the secretagogue sulfonylureas, again a finding that occurred only in women (HR 0.68, 95% CI 0.48 to 0.97).
These "startling differences" in cancer risk between men and women need to be looked at in future studies, the researchers wrote.
Their study also found that there were no differences in risk of bladder cancer between those on a thiazolidinedione and those on other drugs. The FDA has warned that the TZD pioglitazone (Actos) may carry an increased risk of bladder cancer.
They cautioned, however, that the findings may be confounded by the limited number of incident bladder cancers seen in the study.
Kashyap and colleagues concluded that their findings "reflect the body of literature that supports the favorable influence of insulin sensitizers compared with the potential detrimental effects of insulin secretagogues, particularly in a hyperglycemic milieu."
The researchers reported no conflicts of interest.
Diabetes Obesity & MetabolismSource Reference: Sun GEC, et al "Gender-specific effects of oral hypoglycemic agents on cancer risk in type 2 diabetes mellitus" Diab Obesity Metab 2013.