According to research published early online in the American Journal of Gastroenterology, use of metformin may be associated with a decreased risk of pancreatic cancer (seen only in women), whereas use of sulfonylureas and of insulin may increase the risk.

The authors note that pancreatic cancer is relatively rare but is associated with a high mortality.  Major risk factors identified include older age and smoking; minor risk factors include alcohol consumption, dietary factors and obesity.  The association between type 2 diabetes and pancreatic cancer is complex and it is possible that short-term diabetes is a consequence of early pancreatic cancer rather than a cause.  Previous research on the association between use of diabetes medications and pancreatic cancer have suggested metformin may be associated with a decreased risk and sulfonylureas and insulin an increased risk; they have however had a number of limitations.  The purpose of the current study was to explore these possible associations further.

Researchers conducted a large case–control analysis using the UK-based General Practice Research Database (GPRD).  They identified 2,763 cases – i.e. those with a first diagnosis of pancreatic cancer within the study period (1995-2009) - and matched these with six controls each, based on calendar time, age, sex, general practice, and number of years of active history in the GPRD before the index date.  Patients with alcoholism, HIV, or those with less than 3 years of data available before the index date were excluded.  Exposure to insulin, metformin, sulfonylureas, thiazolidinediones, glinides, and glucosidase inhibitors before the index date was assessed for cases and controls.

The main findings reported were as follows:
 
• Long-term use (≥30 prescriptions) of metformin was not associated with a change in risk of pancreatic cancer overall (adjusted odds ratio (OR) 0.87, 95% CI 0.59–1.29)

• Long-term use of metformin was however associated with a decreased risk of pancreatic cancer in women (OR 0.43, 95% CI 0.23–0.80).

• Use of sulfonylureas (≥30 prescriptions, OR 1.90, 95% CI 1.32–2.74) and of insulin (≥40 prescriptions, OR 2.29, 95% CI 1.34–3.92) was associated with an increased risk of pancreatic cancer.

The authors comment that the gender effect seen with metformin was ‘somewhat unexpected’ and should be interpreted with caution as it is based in a limited number of exposed cases and controls, and since there is no obvious explanation.  The increased risk of pancreatic cancer associated with long-term use of sulfonylureas and insulin has been observed in previous studies; however these results were again based on a limited number of exposed cases and controls and require careful interpretation.  They go on to discuss the strengths and limitations of their study.