Matthew Mintz, MD, Internal Medicine, 10:04AM Apr 29, 2013
There has been increased noise recently about the safety of anti-diabetic agents that work on the GLP pathway, specifically the GLP-1 agonists like exenatide and liraglutide and the DPP4 inhibitors such as sitagliptin, saxagliptin, linagliptin and the soon to be available allogliptin. As I discussed in my recent post GLP therapies and pancreatitis. Are you concerned? JAMA Internal Medicine published a case controlled study showing that use of GLP-1-based therapies doubled the risk of pancreatitis. In addition, the FDA recently announced that it was investigating reports of possible increased risk of pancreatitis and pre-cancerous findings of the pancreas from incretin mimetic drugs for type 2 diabetes. The consumer watchdog group (who previously petitioned the FDA to remove linagliptin) recommended removing all of these drugs from the market.
However, finally, the first of its kind trial called "Comparative safety and effectiveness of sitagliptin in patients with type 2 diabetes: retrospective population based cohort study" was just published in BMJ. This was a retrospective analysis of a large database of US insured patients. The cohort included 72, 738 new users of oral antidiabetic drugs (8032 (11%) used sitagliptin; 7293 (91%) were taking it in combination with other agents) followed for a total of 182 409 patient years. The primary outcome was hospital admission and all cause mortality. The authors found no increased risk with sitagliptin use. More importantly, there were two additional findings. First, unlike smaller studies and meta-analysis previously reported, there was no link with pancreatitis. Secondly, there seemed to be a difference in outcomes with patients taking metformin plus a sulfonylurea vs. metformin plus sitagliptin, suggesting that sitagliptin is a better (or at least safer) add on therapy to metformin.