Medscape Medical News > Conference News > DDW 2024
Damian McNamara, MA
May 23, 2024
WASHINGTON, DC — In contrast with a previous study that found glucagon-like peptide 1 (GLP-1) receptor agonists associated with an increased risk for acute pancreatitis and bowel obstruction, a new retrospective study found no significant link to these complications. The new data did, however, reinforce an association between GLP-1s and gastroparesis and biliary disease, specifically gallstones.
One of the big differences from the previous study, published in JAMA in October 2023 by Sodhi and colleagues, is that the current research was able to account for initial body mass index (BMI), said Benjamin Liu, MD, a resident in internal medicine/gastroenterology and hepatology at Case Western Reserve University School of Medicine, Cleveland, Ohio.
This is important, he explained in his presentation (abstract 1074) at the Digestive Disease Week 2024, because obesity on its own is associated with an increased risk for some of these gastrointestinal (GI) outcomes.
“They did an excellent study,” Liu said. “But their platform did not allow them to match participants for BMI.”
Another distinction between the two studies is that the JAMA study excluded people who had diabetes 90 days before or 30 days following the start of GLP-1 therapy.
Instead, Liu said, he and colleague Gengqing Song, MD, “just made it simple” and excluded anyone with diabetes or an A1c ≥ 6.5.
We didn’t want participants with diabetes because “we were looking at GLP-1s for weight loss,” Liu explained.
Although some clinical trials have already assessed adverse events of these medications, “clinical trials are not always a perfect representation of the real world,” Liu told Medscape Medical News. “So, it’s important to do real-world studies to see just what actually goes on.”
Reassessing GI Complications
In the current study, the researchers identified 105,793 patients from the TriNetX healthcare database taking a GLP-1, either semaglutide or liraglutide, for weight loss and 8794 patients taking 8 mg naltrexone/90 mg bupropion. After propensity matching, including for BMI, there were 8792 patients in each group.
They were identified in the database between 2011 and 2023. Researchers noted their first-ever occurrence of acute pancreatitis, bowel obstruction, gastroparesis, or biliary disease during the study period.
Participants had a BMI ≥ 30 kg/m2. In addition to BMI, propensity score matching included demographics, alcohol use, smoking, hyperlipidemia, and abdominal surgery. A second analysis specifically did not match participants for BMI.
The researchers found no significant association between GLP-1s and acute pancreatitis (adjusted hazard ratio [HR], 1.19; 95% CI, 0.66-2.14).
The labeling for semaglutide and liraglutide warns about an increased risk for acute pancreatitis, “but real-world studies and clinical trials are increasingly suggesting there is no increased risk,” Liu said.
They also did not find a significant association between GLP-1s and bowel obstruction (HR, 1.30; 95% CI, 0.69-2.18).
Despite the current findings, more research — especially prospective data — is needed to confirm pancreatitis as well as other GI risks like bowel obstruction potentially associated with GLP-1s, he added.
The study did, however, find an elevated risk for biliary disease (HR, 1.27; 95% CI, 1.02-1.59) in the BMI-matched cohorts.
This could be due to the rapidity of weight loss, Liu suggested. We found that semaglutide caused more weight loss at 6 and 12 months than naltrexone/bupropion, and it did so at a faster rate.
“That falls in line with other data that suggest if you lose weight too fast, you actually have an increased risk of gallstones,” he said.
Rapid weight loss can release cholesterol into the body, which then collects in the bile ducts and causes gallstones. This risk for gallstone formation with rapid weight loss is also seen after bariatric surgery, Liu said.
Without BMI matching, he noted, the increased risk for biliary disease was no longer significant (HR, 1.21; 95% CI, 0.96-1.52).
The researchers also reported a significant association between GLP-1s and gastroparesis (HR, 2.30; 95% CI, 1.19-4.46), confirming the results of the JAMA study “but at a much lower incidence rate once we excluded all patients with diabetes,” said Liu. The JAMA study had a HR of 3.67 for gastroparesis (95% CI, 1.15-11.90).
Weighing in on the Results
“Overall, their study design looks sound,” said Mahyar Etminan, PharmD, an associate professor of medicine at the University of British Columbia in Vancouver and an author of the JAMA study. He agreed that Liu’s research confirmed their findings about gastroparesis and biliary disease.
However, “I interpret the results with intestinal obstruction and pancreatitis as more inconclusive than no risk,” he added.
Session co-moderator and gastroenterologist and motility specialist with Stanford Health Care in California, Linda Anh Bui Nguyen, MD, commented that she thinks “it’s a promising study.” “But with any retrospective study where you’re looking at ICD-10 [International Classification of Diseases, Tenth Revision] codes, it really depends on the coders. The code could be subjective and could be wrong,” said Nguyen, who is also a clinical professor of medicine at Stanford Medical School, California.
For example, the diagnosis of gastroparesis requires a normal endoscopy and a gastric emptying test. “But we find that, frequently, patients are being given a diagnosis of gastroparesis without the test,” she said.
An unanswered question also remains regarding how pancreatitis or biliary disease is being diagnosed: “Was it imaging, lab testing, or symptoms?” she told Medscape Medical News. “For example, if patients had pain on the right side, did they call it biliary?”
Nguyen added that it is difficult to get this kind of detail in retrospective studies. She also agreed with Liu that prospective studies are warranted.
The study was independently supported. Liu, Etminan, and Nguyen had no relevant financial disclosures.
Damian McNamara is a staff journalist based in Miami. He covers a wide range of medical specialties, including infectious diseases, gastroenterology, and critical care. Follow Damian on X @MedReporter.
Leave a Reply