Antidiabetic therapy may affect risk of pancreatic cancer

A case-control study from a large US cancer centre suggests that treatment of diabetes may affect risk of pancreatic cancer, metformin reducing it and insulin and sulphonylureas increasing it.

Patients with type 2 diabetes seem to be at increased risk of several cancers, and there is evidence that it may have a role in pancreatic cancer. Other studies have suggested that metformin reduces and insulin and sulphonylureas increase risk of any cancer, but have not examined the risk of pancreatic cancer specifically. The authors of this paper used data from an existing case-control study that is ongoing at their institution (University of Texas M. D. Anderson Cancer Centre) to study the potential association. This study started in 2004 and aimed to define environmental and genetic factors that contribute to the development of pancreatic cancer.

Cases were consecutively recruited from patients with newly diagnosed and confirmed pancreatic ductal adenocarcinoma seen at the Centre. Controls were recruited from healthy individuals accompanying patients being treated at non-gastrointestinal centres within the institute: they were spouses and non-related relatives and friends of patients with cancers other than gastrointestinal or smoking-related. They were matched by age (+/- 5yr), sex, and race. Neither cases nor controls had a previous cancer history except for non-melanoma skin cancer. Diagnosis of diabetes, and frequencies of use of insulin, insulin secretagogues, metformin, and other antidiabetic medications among diabetic patients were compared between cases and controls. The risk of pancreatic cancer was then estimated using unconditional logistic regression analysis.

There were 973 cases (259 diabetic) and 863 controls (109 diabetic); the two groups were generally comparable except that cases included more black people and people aged over 70. After adjustment for potential confounding factors, diabetics who had taken metformin had a significantly lower risk of pancreatic cancer compared with those who had not (odds ratio[OR], 0.38; 95% CI, 0.22 to 0.69; P = 0.001). The association remained present when analysis was restricted to those with a duration of diabetes >2 years, and those who had never used insulin (OR 0.44; 95% CI, 0.22 to 0.87; and OR, 0.41; 95% CI, 0.19 to 0.87 respectively). Diabetics who had taken metformin also had a lower risk than non-diabetics (OR, 0.38; 95% CI, 0.21 to 0.67; P = .001), however the difference between non-diabetics and diabetics who had taken insulin secretagogues was not significant.

Diabetics who had used insulin or taken insulin secretagogues had a significantly higher risk of pancreatic cancer than diabetics who had not (OR, 4.99; 95% CI, 2.59 to 9.61; P<0.001; and OR, 2.52; 95% CI, 1.32 to 4.84; P=0.005, respectively).

The authors conclude that in this study population, patients with type 2 diabetes who had used metformin, especially for >5 years, had a significantly reduced risk of pancreatic cancer compared to never users. Additionally, although the numbers were smaller and therefore the confidence intervals wider, there was also an indication that use of insulin or insulin secretagogues was associated with an increased risk. They caution that although the overall study had a large sample size, statistical power was limited for diabetic subjects only: as a result, they consider that the observations need to be confirmed in larger studies.

An accompanying editorial discusses the study.

Gastroenterology 2009; 137: 482–8 (link to abstract, full text available free at time of posting); Gastroenterology 2009; 137: 412-5 (link to full text, available free at time of posting); from Medscape for 18th August 2009 (free registration required)