GLP-1 RA boom to have ‘major impact’ on gastroenterology


By Geir O'Rourke

9 Nov 2023

Booming uptake of GLP-1 receptor agonists has potential to dramatically expand demand for gastroenterology services because of links with adverse events such as gastro-oesophageal reflux disease, it is being warned.

Coming as demand for the medicines continues to grow in use for diabetes and obesity, the message follows research linking shorter-acting GLP-1 RAs with increased risk of a range of gastroenterological conditions.

Some 177,000 patients on GLP-1 RAs for T2DM were included in the retrospective study, which used records from the TriNetX anonymised global database and included a similar number of matched controls on SLGT2i, thiazolidinediones (TZD) or a sulfonylurea.

This revealed that, compared to the controls, patients starting therapy had an 11% increased risk of a new diagnosis of GORD, with the proportion developing erosive disease more than doubling (13% vs 6%), the researchers reported in Gut (link here).

They stressed the impact appeared to be concentrated in those patients exposed to lixisenatide, exenatide and liraglutide, which were associated with a 22% increased risk of erosive reflux disease and a 28% increased risk of oesophageal stricture.

Patients taking the short-acting GLP-1 RAs were at even greater relative risk of developing Barrett’s with or without dysplasia (up 37% and 51% respectively).

But importantly, the 132,000 patients on long-acting semaglutide and dulaglutide were at no greater risk of developing any of these conditions than the controls, reported the researchers.

Nevertheless, the implications for gastroenterology workloads were likely to be significant, wrote gastroenterologist Dr Benson Massey of the Medical College of Wisconsin in an accompanying editorial (link here).

“Public awareness of these drugs is increasing, particularly from extensive television advertisement in the USA,” he noted.

“Indeed, the demand has become so great that formulations of GLP-1 RAs approved in the USA for treating diabetes are being used off-label to treat obesity, resulting in shortages for patients needing them for glycaemic control.”

And given patients with obesity were becoming the dominant target group for these agents, there needed to be a better objective assessment of the baseline burden of reflux disease and how GLP-1 RAs affected this, he said.

Questions which needed to be addressed included whether the medicines triggered more postprandial transient lower oesophageal sphincter relaxations and how baseline gastric emptying affected GORD amongst others.

Indeed, there may be some need for patients at higher risk of GORD to be placed prophylactically on anti-reflex therapy when starting GLP-1 RAs, Dr Massey noted.

Another consideration was the impact of delayed gastric emptying on endoscopy, which raised issued on whether standard instructions for pre-procedure fasting to be adjusted.

“The expanded demand for consultation and endoscopy to evaluate new symptoms will be followed by downstream interventions to monitor and manage identified complications,” he added.

“Rather than offering an alternative to bariatric surgery, side effects from these agents may push more patients towards gastric bypass, which can also treat GORD.”

“For the individual patient, gastroenterologists should review use of these agents (including non-prescription) when evaluating new or worsening GORD symptoms, particularly when nausea or vomiting is also present.”

“Patients with pre-existing GORD should be counselled about the possibility of symptom escalation.”

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