For patients taking GLP-1 receptor agonists (GLP-1 RAs), the use of proton pump inhibitors (PPIs) is associated with an increased risk for gastrointestinal (GI) adverse effects, according to research presented at the Society of General Internal Medicine (SGIM) 2026 Annual Meeting in Washington, DC.
Side effects of GLP-1 drugs commonly include nausea, vomiting, and delayed gastric emptying that can lead to heartburn and sulfur burps, all which mimic symptoms of gastroesophageal reflux disease (GERD). PPIs are commonly prescribed to treat GERD.
“A lot of patients are on PPIs and GLP-1s at the same time,” said Mustafa Naveed, DO, internal medicine resident at Carilion Clinic, Virginia Tech Carilion School of Medicine in Roanoke, Virginia, who presented the poster. “PPIs can be prescribed unnecessarily sometimes, or for an extended amount time often longer than necessary…and I wanted to look into whether that kind of combination of prescription medications is making things worse.”
An estimated 1 in 8 US adults use GLP-1 RAs, which are used to treat type 2 diabetes and obesity. Although GLP-1 use has become more common, clinicians are still trying to understand the myriad of interactions the drugs have with other oral medications.
Patients who took GLP-1s and PPIs concurrently were more than twice as likely to experience adverse effects of the upper GI (risk ratio [RR], 2.37; 95% CI, 2.30-2.44; P <.001) than those taking GLP-1s alone, according to findings from an analysis of data from more than 1.2 million adults in the TriNetX Research Network over a 20-year span starting in 2005. The analysis showed approximately 18% of these patients had an active prescription for a GLP-1s and a PPI.
Using propensity score matching, 395,082 adults (60.9% women; 67.4% White; average age, 58 years) were included who were prescribed a GLP-1 RA, half of whom also had a prescription for a PPI.
Nausea and vomiting were nearly twice as likely to occur for patients who took both medications than for those who took GLP-1s alone (RR, 1.81; 95% CI, 1.75-1.88; P < .001). They were also almost four times more likely to experience indigestion (RR, 3.50; 95% CI, 3.28-3.75; P < .001). Patients taking both medications were three times as likely to develop acute pancreatitis and almost twice as likely to develop gallstones (P < .001).
Lower GI side effects were also more common for those taking both drugs, including diarrhea, constipation, and obstruction or temporary stoppage of intestinal movement (RR, 2.62; 95% CI, 2.33-2.93; P < .001).
Patients taking both medications were five times as likely to need exploratory procedures such as upper endoscopy than those who were just on GLP-1s.
Because of the invasive nature of the procedure, “deprescribing both PPIs and GLP-1s to see what is causing the symptoms before moving onto endoscopy would definitely be beneficial,” Naveed said.
Karthik Ravi, MD, a gastroenterologist at Mayo Clinic in Rochester, Minnesota, said the results should be interpreted cautiously, as de-identified data limit what is known about why a patient is on a PPI and the specific type of GLP-1, since short- and long-acting versions have different side effects. Ravi said, patients on PPIs might have GI-related issues independent of GLP-1 use.
“All this tells me is that patients who are on GLP-1s and have GI symptoms are more likely to be on a PPI,” Ravi said.
Naveed said, his recommendation is for clinicians is to follow a recent push to deprescribe PPIs or try shorter courses of the medication when possible.
“The most important thing is just being conscious and aware of patients that are taking both of these medications, especially when they do present with upper GI or abdominal symptoms, nausea, vomiting, or reflux, and making sure that we kind of cover all of our bases,” Naveed said. “We need to continually evaluate our patients to see if they really need to be on these [PPI] medications.”
To help patients ease heartburn and other upper GI adverse side effects associated with GLP-1 use, Ravi said, he will continue to prescribe PPIs for patients, but believes this study indicates a need for further study into how the two medications function together.
“If you’re having heartburn, let’s treat it. I worry that a study like this, where a patient starts with a GLP-1, they have bad heartburn, and now you’re making providers afraid to put them on a PPI because you think it’s going to make it worse — that’s probably not helpful,” Ravi said.
The study received no external funding. Naveed and Ravi reported having no relevant financial disclosures.
No comments:
Post a Comment
Note: Only a member of this blog may post a comment.