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.

Comments

Post a Comment

if you would like to receive the near-daily emails regularly, please email me at gmodest@uphams.org

Popular posts from this blog

HDL a negative risk factor? or cholesterol efflux??

Although the data on HDL being protective of atherosclerotic disease is pretty consistent, there are negative studies, and the data on medications which dramatically improve HDL levels (eg, the cholesteryl ester transfer protein --CETP --inhibitors, such as torcetrapib) are clinically disappointing. there have been several explanations for this. for example, some HDL particles are "pro-inflammatory" and elicit an atherosclerotic response (which may be related to apolipoprotein C-III). a new article in NEJM highlights another angle -- that the issue is not the HDL number, but HDL's functionality in the reverse transport of cholesterol, as measured by the cholesterol efflux capacity (see  lipids HDL efflux capacity vs amt NEJM 2014 in dropbox, or  DOI: 10.1056/NEJMoa1409065). This article looks at the Dallas Heart Study, where they measured HDL levels, HDL particle concentrations, and cholesterol efflux capacity in 2924 adults free of cardiovascular disease and followed p
Read more

Drug company shenanigans: narcolepsy drug

I have not done a blog for a long time on drug company shenanigans. So it is my great pleasure to bring up a brand-new drug company approach to garner huge amounts of money (see  https://www.nytimes.com/2023/02/28/business/jazz-narcolepsy-avadel-patents.html?smid=nytcore-ios-share&referringSource=articleShare  ).  Based on an article by  Rebecca Robbins of the New York Times, who has written several articles on drug company excesses   As background, this will be my 42 nd  such blog: for the array, see  https://bucommunitymed.wpengine.com/page/4/?s=drug+company+shenanigans   Th e drug company  approach  this time  to extending  their  patents has a few “interesting” angles: -- this is a medication manufactured by Jazz Pharmaceuticals to treat narcolepsy: there are 2 versions: Xyrem and Xywav (Xywav has less sodium, so is marketed to those who should be on a low sodium diet). These meds are basically derivatives of gammahydroxybutyric acid (GHB)      -- the drug actually has a pretty
Read more

UPDATE: ASCVD risk factor critique

  I decided to do an extensive update of my prior ASCVD (atherosclerotic cardiovascular disease) risk analysis and critique of risk calculators, with much more information about the “non-traditional” risk factors. I felt that there should be more data/clarification, since I think we are really undertreating/not preventing the most common cause of death by relying on the ASCVD risk calculators   -- Cardiovascular risk models:      -- many of us rely on the various cardiovascular risk models to determine the appropriate approach to patients, and these are often integrated into the electronic medical records      -- these risk models have several very important limitations:          -- they are typically based on community data, eg from the Framingham study etc. But, in clinical practice, we are dealing with the individual and not the community:              -- there is very clear evidence that there are many individual risk factors that are associated with increased risk of a cardiovascu
Read more