exenatide and pancreatitis FDA/EMA assessment

of all of the new diabetes meds, the one i am most impressed with is exenatide. mostly because the long-acting preparation is injected only once a week, has studies showing it is at least as good an effect as lantus in patients without endstage diabetes, and is pretty physiologic (stimulates postprandial insulin release and decreases appetite, so unusual to be hypoglycemic and tend to lose weight). that being said, none of the new meds have real clinical outcome data, just surrogate marker of A1C improvement (as does rosiglitazone, which we know is associated with increased heart disease). one concern with GLP-1 agonists such as exenitide is that a couple of studies suggested increased risk of pancreatitis, and even some concern about pancreatic cancer. in this light, the FDA and EMA (european medicines agency) independently investigated and came out with a safety assessment (see dm exenatide and pancreatitis FDA statement 2014 in dropbox, or DOI: 10.1056/NEJMp1314078).  their conclusions after reviewing all of the human and animal data so far, including postmarketing info:

--animal toxicology studies (healthy animals, those with diabetes, and those with pancreatitis) -- no evidence of any exenitide-induced pancreatitis
--human studies -- "may" be slight increase in amylase/lipase, but within normal range. asymptomatic. the incidence of pancreatic cancer was actually lower in patients on a DPP-4 antagonist (which decreases the degradation of endogenous GLP-1). both FDA and EMA found the observational data suggesting a relation with pancreatitis to have methodologic shortcomings (limited power, inadequate outcome verification, inadequate confounding control)

so, although the FDA and EMA "have not reached a final conclusion at this time regarding a causal relationship", both agencies feel that the current data do not support a real association, though both agencies will continue to consider pancreatitis  "a risk associated with these drugs until more data are available".  i have used the exenitide on a few patients so far. some GI intolerance, but generally impressive results.

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