Oral Insulin Sensitizers Associated With Decreased Cancer Risk in Women With Type 2 Diabetes


Key Points

  • Agents that increase endogenous insulin levels may promote carcinogenesis.
  • Women on a thiazolidinedione, an insulin sensitizer, had a 32% lower risk of cancer compared with those on a sulphonylurea, an insulin secretagogue.
  • In women who received insulin sensitizers, there was a 21% reduced risk of cancer compared with women who received insulin secretagogues.

According to the findings of a meta-analysis by Sun et al published in Diabetes, Obesity, and Metabolism, patients with type 2 diabetes mellitus who are on certain therapies, such as insulin secretagogues, may be at higher risk for cancer. This increased risk was seen more frequently in women, and oral diabetes therapy did not appear to show significant difference in men.

Study Methodology

Current research in cancer prevention has centered on comorbidities that may increase an individual’s likelihood of developing cancer. One such comorbidity is diabetes mellitus, in which factors such as hyperglycemia and insulin resistance have been shown to increase the risk of malignancy.

To determine the effect of diabetes therapy on the risk of cancer, the investigators analyzed the medical records of 25,613 patients with diabetes mellitus from the Cleveland Clinic Diabetes Registry from the period 1998 to 2006. These records were cross-matched to the clinic’s database of 48,051 patients with cancer. Patients were followed until the date of the first new malignancy, date of death, or date of last visit.

Patients with diabetes mellitus were prescribed one of four oral agents: biguanides (metformin), sulphonylureas (glimepiride, glipizide, and glyburide), meglitinides (repaglinide and nateglinide), or thiazolidinediones (rosiglitazone and pioglitazone). Patients on multiple agents were not eligible for study. Additional analyses were performed to compare thiazolidinediones vs biguanides and insulin sensitizers (biguanides and thiazolidinediones) vs insulin secretagogues (sulphonylureas and meglitinides).

Significant Findings

Of the total number of patients studied, 892 were identified to have cancer. The overall cancer rate per 100,000 was 952 for men and 802 for women. In total, the rate of cancer occurrence was 39% higher in men and 56% higher in women in the diabetes cohort. In addition, a greater percentage of the patients in the cancer cohort were treated with a sulphonylurea than with a biguanide (P < .01).

Although there was no difference in the results regarding the specific diabetes therapy taken by men, there was a significant difference among women. Women receiving thiazolidinedione had a 32% lower risk of cancer than did those taking sulphonylurea (hazard ratio [HR] = 0.68; 95% confidence interval [CI] = 0.48–0.97). In addition, the investigators noted a 21% reduced risk of cancer in women who received insulin sensitizers compared with those who received insulin secretagogues (HR = 0.79; 95% CI = 0.64–0.98).

Prostate cancer and breast cancer were the two most common cancer sites in the diabetes cohort, accounting for more than 25% of the total cancers. Other common cancers included lung, kidney, and colorectal malignancies.

Clinical Implications

The results of this current study are consistent with previous studies suggesting that increasing levels of endogenous insulin may promote carcinogenesis. The investigators noted that the findings of their study “highlight the gender-specific impact of oral diabetes therapy on cancer risk.” Women taking oral hypoglycemic therapies were found to have a lower risk of cancer, and agents that augment endogenous insulin levels were associated with a higher risk of cancer in women.

Thus, the results from this study would lead clinicians to favor insulin sensitizers such as biguanides and thiazolidinediones over insulin secretagogues such as sulphonylureas and meglitinides. In particular, thiazolidinedione therapy was shown to decrease the risk of certain cancers, such as bladder cancer and lung cancer.

In closing, the investigators stated, “As people with diabetes are living longer and surviving heart disease, cancer is really a big health issue. Doctors need to be informed that diabetes drugs and diabetes pathophysiology can impact cancer.”

Sangeeta R. Kashyap, MD, of the Cleveland Clinic Foundation, is the corresponding author of the article in Diabetes, Obesity, and Metabolism.

This study was funded in part by the Cleveland Clinic Lerner College of Medicine Research Programs. Study author Michael W. Kattan, PhD, received funding from Astra Zeneca for generation of the diabetes registry and is a consultant for Merck and GlaxoSmithKline. Robert Zimmerman, MD, is a speaker for Novo Nordisk.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.