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Sulfonylurea or Exogenous Insulin Use May Increase Cancer Risk in Type 2 Diabetics: Presented at ADA

By Jill Stein

SAN DIEGO, CA -- June 14, 2005 -- Exposure to sulfonylurea and exogenous insulin is associated with a significantly increased risk of cancer-related mortality compared with exposure to metformin, Canadian researchers reported here on June 14^th at the American Diabetes Association's 65^th Annual Scientific (ADA).

It is uncertain whether this increased risk is related to a protective effect of metformin or a deleterious effect of sulfonylurea and insulin, said Samantha L. Bowker, MSc, research associate, Institute of Health Economics, Edmonton, Alberta, Canada, and colleagues.

"There is a well-established link between type 2 diabetes and cardiovascular disease, which is reflective of the features of metabolic syndrome and characterized by insulin resistance," Ms. Bowker observed.

The metabolic syndrome is associated with dyslipidemia, hypertension, insulin resistance/hyperinsulinemia, and adiposity.

Evidence from cellular models, animal models, and epidemiologic studies suggest that insulin has mitogenic properties, and that insulin resistance and hyperinsulinemia are associated with tumor growth or carcinogenesis, she added.

Research suggests that therapeutic agents that increase circulating insulin levels might promote tumor development and increase cancer-related mortality, she explained.

The researchers conducted their study based on the hypothesis that exposure only to sulfonylureas and exogenous insulin would have an increased risk of cancer-related mortality compared with exposure to therapies known to enhance insulin activity, such as metformin.

The study used administrative databases from Saskatchewan Health to identify new users of metformin or sulfonylureas from January 1, 1991 to December 31, 1996, with follow-up until death, departure from the province, or December 31, 1999. Overall, they identified 10,309 new users of metformin or sulfonylureas, who were subsequently followed for a mean of 5.4 years.

They compared cancer-related mortality between groups of patients who used metformin alone or in combination with sulfonylurea, and sulfonylurea monotherapy users.

Unadjusted cancer mortality was 4.9% in 3340 sulfonylurea monotherapy users and 3.5% in 6969 metformin users (P =.001).

After adjusting for age, sex, and insulin use, the sulfonylurea cohort had a significantly high cancer-related mortality rate compared to the metformin cohort (hazards ratio: 1.3; P =.012). Insulin use was associated with an adjusted hazard of cancer-related mortality of 1.9, (P <.0001).

"Despite the increasing recognition of the link between type 2 diabetes and cancer, very little is known about the possible effect of various antidiabetic therapies in cancer-related mortality," Ms. Bowker commented. "The pharmacologic effects of these treatments on circulating insulin levels may play an important role in the comorbidity relationship."

Finally, she said that it is uncertain, based on her group's data, whether the observed increased risk of cancer-related mortality is related to a protective effect of metformin or a deleterious effect of sulfonylureas and insulin, although based on the available literature, her group suspects that the latter is the case.


[Presentation title: Increased Cancer-Related Mortality for Patients With Type 2 Diabetes Who Use Sulfonylureas or Exogenous Insulin Compared to Metformin. Abstract 521-P]

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