Five Things to Know About Weight-Loss Drugs and IBD

As gastroenterologists seek better therapies for inflammatory bowel disease (IBD), they’re closely watching the evolving data on GLP-1 receptor agonists. Could drugs like semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound) turn the tide against ulcerative colitis and Crohn’s disease?

Here are five things to know:

Early Data for GLP-1 Drugs in IBD Are Encouraging

Research into GLP-1 medications and IBD is still at an early stage, and gastroenterologists aren’t recommending that they be used outside their FDA-approved indications such as obesity and type 2 diabetes.

“These drugs should not be viewed as IBD therapies yet,” Sailish Honap, MD, MBBS, of St. George’s University Hospitals NHS Foundation Trust in London, told MedPage Today. “However, for patients who already have an approved indication, such as obesity or type 2 diabetes, current evidence supports their use with appropriate monitoring.”

The data so far about the effects of the drugs on IBD are both reassuring and intriguing, he said. Studies have shown that “GLP-1 receptor agonist use in patients with IBD is not associated with worsening disease and may be linked to lower rates of corticosteroid use, hospitalization, or surgery in some populations.”

In an interview, Aakash Desai, MD, of Allegheny Health Network and Drexel University College of Medicine in Pittsburgh, highlighted his team’s 2024 retrospective cohort study of patients with IBD and type 2 diabetes, which suggested an association between use of GLP-1 drugs and a reduced risk of IBD-related surgery in patients with ulcerative colitis (adjusted HR 0.37, 95% CI 0.14-0.97) and Crohn’s disease (aHR 0.55, 95% CI 0.36-0.84) compared with controls taking oral hypoglycemic agents.

A recent study presented at the Crohn’s & Colitis Congress also linked GLP-1 drugs to better outcomes in IBD patients, with improvements in corticosteroid dependence, hospitalizations, and mortality.

“I have not seen any patients have flare of their IBD after starting a GLP-1,” Desai added, although he noted that most of these patients began weight-loss treatment while in remission.

Adverse Effects From GLP-1 Drugs Don’t Appear More Common in IBD

As for adverse effects, gastroenterologists said they don’t appear to be more common in patients with IBD.

“Overall, I have seen patients tolerate these medications well,” Desai said. “GI side effects are common, typically mild, and usually improve/resolve with dose adjustments. They are not higher than in patients without IBD.”

Even bowel obstruction, a known risk of GLP-1 drugs, doesn’t seem to be more likely in patients with Crohn’s disease, Parakkal Deepak, MBBS, MS, of Washington University School of Medicine in St. Louis, told MedPage Today. Intestinal blockage is a known risk of Crohn’s.

Weight-Loss Drugs May Improve IBD in Different Ways

Why do GLP-1 agonists seem to be helpful in reducing IBD symptoms? One key factor appears to be its impact on weight.

“Obesity itself can worsen outcomes in IBD,” Honap said. “It is associated with systemic inflammation, worse surgical outcomes, impaired quality of life, and may affect the pharmacokinetics of IBD therapies. So weight loss and improved metabolic health alone could plausibly improve IBD-related outcomes.”

But the effect may go beyond the benefit of shedding pounds. The drugs “may have direct effects relevant to IBD biology,” Honap noted. “Preclinical data suggest beneficial effects on pathways that are important in the pathophysiology of IBD — specifically with relevance to immune signaling, epithelial barrier function, and microbial dysbiosis.”

On another front, patients may change what they eat, he added. “Since diet can influence symptoms, microbiome composition, and inflammation, that could be another indirect mechanism.”

Certain Patients Should Be Extra-Cautious About GLP-1 Drugs

Without data to guide them, gastroenterologists are hesitant to prescribe weight-loss drugs in patients with normal or below-normal weight because of the risk of unnecessary weight loss.

“I would probably not recommend using this in a normal-weight IBD patient with the intent of controlling a disease flare,” Deepak said.

Honap noted that he would be cautious about use of the drugs in patients with severe gastrointestinal disease, previous pancreatitis, significant biliary disease, severe renal impairment, severe hepatic impairment, or personal/family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndromes.

“I would also be cautious in patients at risk of malnutrition or sarcopenia, particularly those with active Crohn’s disease or recent weight loss,” he said. “For patients on thiopurines or other oral therapies, and for those undergoing substantial weight loss while on biologics, closer monitoring may be needed because drug exposure could change.”

However, Deepak cautioned that patients undergoing colonoscopy or endoscopy should stop the drugs for a week before the procedures in order to lower their risk of aspiration. The drugs slow digestion, so a day of fasting may not fully empty the stomach.

He also noted that there have been reports that patients on GLP-1 drugs are at increased risk of poor bowel preparation prior to colonoscopy, meaning they may need more extensive colon-emptying regimens.

Prospective Trials Are Underway for GLP-1 Drugs in IBD

Deepak highlighted a pair of ongoing phase IIIb studies that are examining whether patients with Crohn’s disease or ulcerative colitis and obesity/overweight fare better on the IBD drug mirikizumab (Omvoh) and tirzepatide versus mirikizumab and placebo. The studies are expected to end in 2028.

Deepak himself is part of a team that’s launched a phase II trial that will examine the effects of tirzepatide versus standard care in patients with overweight/obesity and Crohn’s disease. The study began a year ago, is expected to enroll 60 patients, and is scheduled to end by August 2028.