Spotlight on incretin-based drug side effects
medwireNews: Two studies in JAMA Internal Medicine seek to quantify infrequent side effects associated with use of incretin-based drugs in patients with Type 2 diabetes in general practice.
The first study, by Laurent Azoulay (McGill University, Montreal, Quebec, Canada) and co-workers, used data for 71,369 patients identified in the UK Clinical Practice Research Datalink (CPRD) to assess the risk of bile duct and gallbladder disease.
They found, in line with randomised controlled trial (RCT) findings, that patients using glucagon-like peptide (GLP)-1 analogues had an increased risk of these outcomes compared with those using two or more other oral antidiabetic agents, at rates of 6.1 versus 3.3 per 1000 person–years.
The risk was highest during the first 180 days of use, at an incidence rate of 6.8 per 1000 person–years. The incidence fell with longer duration of use, to around five cases per 1000 person–years, which was not significantly higher than for use of other antidiabetic drugs.
Use of dipeptidyl peptidase (DPP)-4 inhibitors, by contrast, was not associated with the incidence of bile duct and gallbladder disease, regardless of duration of use.
For the second study, a different research team also headed by Azoulay addressed the risk of acute pancreatitis in 1,532,513 patients from five Canadian provinces, the US MarketScan research database and the UK CPRD. The researchers found no increased risk with use of either class of incretin-based drug, relative to use of at least two other oral antidiabetics. The risk also did not significantly vary with duration of use.
The purported risk of acute pancreatitis with incretin-based drugs comes from the US Food and Drug Administration adverse event reporting system, with some RCTs and observational studies backing it up, but others, like the current study, finding no association.
Editorialist Peter Butler (University of California, Los Angeles, USA) describes the current study as “impressively large”, but adds that “[t]he absence of pancreatitis associated with GLP-1–based therapy in retrospective analyses, even in a large cohort, falls short of the gold standard, the RCT.”
He says that the overall risk of pancreatitis “seems reassuringly low”, but stresses that “the unresolved concern is whether the relatively low risk of pancreatitis and the more frequently observed increase in lipase levels herald a subclinical proinflammatory effect that in the longer term could increase the risk for pancreatic cancer.”
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