The massive debate over links between the use of incretin drugs (DPP-4 inhibitors and GLP-1RA injectables) and pancreas safety has, to this point, been based on anecdote, controversial science and retrospective cohort analyses. These are all prone to various forms of bias leading, in my view, to the correct analysis and advice from the Federal Drugs Administration, European Medicines Agency (and any other legitimate body that has issued comment) to continue current prescribing.
The addition of some prospective clinical data into this arena is, therefore, very welcome. Two placebo-controlled randomised clinical trials (set up to examine cardiovascular safety) have recently provided results on pancreas outcomes in patients receiving saxagliptin and alogliptin. In the SAVOR-TIMI 53 study there was no significant difference in acute or chronic pancreatitis (pre-specified events of special interest) and no excess risk of pancreatic cancer. Likewise, in the EXAMINE study, incidence of pancreatitis was similar in both active and placebo groups and there were no cases of pancreatic cancer.
Does this make the issue go away? I doubt it. Although the two studies were large (N= 16,492 & 5,380 respectively), they were relatively short and were not powered for pancreas safety end-points. Also, the doubters will point to numerical increases in pancreatitis in the DPP-4 inhibitor treated patient groups. Fortunately more data will be forthcoming and we await results from a further eight placebo-controlled incretin trials, which will include over 66,000 patients, many followed for over five years. Watch this space….
Professor Steve Bain