乌鸦传媒

Postprandial increases in lipase and amylase seen with GLP-1 drugs didn't happen in patients who weren't on those medications, providing a potential mechanism by which the drugs may be linked to pancreatitis, Danish researchers suggested.

In a study of 30 patients, neither of the two enzymes increased after meals in patients with type 2 diabetes or in healthy controls, , of Gentofte Hospital at the University of Copenhagen, and colleagues wrote in a research letter appearing in the .

"Circulating levels of lipase and amylase do not change in the postprandial state, ruling out that plasma lipase and amylase increments are 'natural' responses to endogenous elevations in plasma GLP-1 concentrations," , of Gentofte Hospital, and a co-author on the paper, said in an email to 乌鸦传媒.

"Thus, increments in plasma lipase and amylase seem to constitute a pharmacologic effect of GLP-1RAs, and further studies investigating the underlying mechanisms are highly warranted -- especially seen in the light of recent reports suggesting that incretin-based therapies promote pancreatic inflammation and possibly cell proliferation within the endocrine and exocrine pancreas," Knop said.

The question of whether GLP-1 drugs cause pancreatitis and pancreatic cancer has been hotly debated over the past several years. Studies have drawn conflicting conclusions, although the FDA and the EMA have both ruled that available data do not suggest an increased risk with the drug.

It's been shown in some studies that incretin-based therapies lead to small increases in plasma concentration of amylase and lipase. For instance, in the SCALE Maintenance study that evaluated high-dose liraglutide (Saxenda) at 3 mg for weight loss, median lipase levels increased through the treatment period.

But no one has evaluated whether plasma concentrations of these enzymes increase postprandially in patients who aren't taking these medications.

To assess that question, Sonne and colleagues measured pancreas-specific amylase and lipase before and after four different meals in 15 patients with type 2 diabetes and 15 matched controls.

Those meals included a 75-g oral glucose tolerance test and three isocaloric (500 kcal) and isovolemic (350 mL) liquid meals.

They found that levels of the two enzymes didn't change after the meals, "suggesting that postprandial elevations of endogenous GLP-1 cannot trigger enzyme release from the human pancreas, at least not acutely."

The results suggest that GLP-1 drugs may cause the postprandial increases in amylase and lipase seen in other studies, they concluded, cautioning that the findings are limited to liquid meals. It's not clear if larger or solid meals could induce difference effects.

Knop said the team is also planning to study the effect of GLP-1 drugs on postprandial gall bladder emptying, which may be an important determinant of pancreatitis.

, of the University of Glasgow, who was not involved in the study, acknowledged that the results are interesting, but that "the best clinical data we have to date do not suggest a major pancreatitis signal with GLP-1 agonists."

Sattar pointed to upcoming data from ELIXA and TECOS trials, two large late-stage studies that could further inform the debate about these agents and pancreatitis risk.

"The community should await trials to get the best information possible on the existence, or otherwise, of pancreatitis risk," he said.

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