Oral insulin sensitizers — especially thiazolidinediones (TZDs) — were associated with a significantly reduced cancer risk in women with type 2 diabetes, a new retrospective analysis of 2 large databases finds.
The results, published online December 5 in Diabetes, Obesity, and Metabolism, suggest that insulin-sensitizing drugs should be explored further for their potential in cancer prevention and treatment and to stop cancer recurrence, the study's principal investigator, Sangeeta R. Kashyap, MD, an endocrinologist and associate professor of medicine at the Cleveland Clinic Foundation, Ohio, told Medscape Medical News.
"These drugs...are cheap, widely available, and easy to take when you compare them with chemotherapy," said Dr. Kashyap. The mechanism isn't entirely known but is believed to be related to the growth-factor effects of insulin, she suggested. "So we need to do more research to learn what the growth factors are downstream of insulin that can fuel certain cancers and [whether] drugs like metformin and TZDs [could] be cancer protective," she said.
Previous data have pointed to a cancer-protective effect from metformin, while cancer-related findings for TZDs have been more mixed. And this is the first study to suggest a gender difference, she told Medscape Medical News.
Significant Effect in Women
Data on 25,613 patients in the Cleveland Clinic Diabetes Registry were cross-matched with those of 48,051 cancers in the Cleveland Clinic Tumor Registry for the 8-year period 1998–2006.
Incident cancers were identified in a total of 892 adults (513 women and 379 men) who had been prescribed 1 of 4 types of oral glucose-lowering agents — biguanide (metformin), sulfonylurea (glimepiride, glipizide or glyburide), meglitinide (repaglinide and nateglinide), or TZD (rosiglitazone or pioglitazone). (Patients taking more than 1 oral diabetes drug and those taking other classes of oral diabetes drugs were not included.)
The data reaffirm previous studies showing that cancer is more common among people with diabetes. The overall age-adjusted cancer incidence rate per 100,000 of the diabetes cohort was 952 for men and 802 for women. Those rates are 39% higher in men and 56% higher in women compared with the general US population, the authors report in their paper.
"As people with diabetes are living longer and surviving heart disease, cancer is a really big health issue. Doctors need to be informed that diabetes drugs and diabetes pathophysiology can impact cancer," Dr. Kashyap told Medscape Medical News.
The data were adjusted for 20 variables that are known to be associated with diabetes severity and/or cancer risk, including age, body mass index, HDL and LDL cholesterol, coronary heart disease, race, gender, HbA1c, statin use, income, kidney function, and tobacco use. Separate models were created for men and women.
No significant differences in cancer rates by diabetes medication were seen among the men. This may be because other factors such as age, socioeconomic status, and smoking were such strong cancer risk factors among males that they overshadowed any impact of diabetes drugs, Dr. Kashyap said.
Sex-hormone differences may also play a role, the authors suggest.
Among women, however, those taking insulin sensitizers (TZD or biguanide) had a significant 21% lower risk for cancer compared with those taking insulin secretagogues (sulfonylurea and meglitinide). Even more significant, women who took TZDs had a 32% lower cancer risk compared with those on sulfonylureas.
Oncologists "Very" Interested in Diabetes Drug Effects
The 2 most common cancer sites were prostate (129) and breast (104), accounting for 25% of the total. However, the numbers for each cancer type weren't large enough to generate meaningful data about the relationship to the drugs, she told Medscape Medical News.
In contrast to previous studies showing a link between pioglitazone and bladder cancer, there was no suggestion of that from these data. There were 29 cases of bladder cancer and 122 cases of urinary-tract cancer, but no significant differences in risk were noted between TZD users and non-TZD users for either cancer. Again, though, the numbers were small, the authors acknowledge.
Dr. Kashyap told Medscape Medical News that while no clinical recommendations could yet be made based on this "hypothesis-generating study," physicians should definitely keep an eye on the rapidly emerging data. "Oncologists are very into this now... Their thoughts are that these drugs could be used to prevent recurrence of cancer in people with diabetes. This is a great thing."
Portions of this research were funded by the Cleveland Clinic Lerner College of Medicine Research Programs, and AstraZeneca provided funding for generation of the diabetes registry. Dr. Kashyap has reported no relevant financial relationships. Disclosures for the coauthors are listed in the article.
Diabetes Obes Metab. Published online December 5, 2013. Abstract
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