GLP-1 RAs Tied to Suboptimal Bowel Prep, Repeat Colonoscopy

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), used for diabetes or obesity, are associated with a significantly lower quality of bowel preparation and a greater need for repeat colonoscopy, new research suggests.

"We began observing inadequate bowel preparation in our patients undergoing colonoscopy who were on GLP-1 RAs, which raised questions, especially given the association between these medications and delays in intestinal transit," study investigator Eric. J. Vargas, MD of the Mayo Clinic in Rochester, Minnesota, told Medscape Medical News. The team decided to investigate.

The "most surprising finding" was the "notably higher rate of inadequate bowel preparation, which necessitates a repeat colonoscopy within 12 months to ensure adequate screening and surveillance for colorectal cancers," he said. "Specifically, for every 14 patients treated with GLP-1 RAs, one patient would require a repeat colonoscopy due to suboptimal preparation."

In light of the findings, "clinicians should consider patients on GLP-1 RAs to be a population at risk for poor quality of bowel preparation," he said.

The study was published onlineon October 19 in the American Journal of Gastroenterology.

Low Prep Scores

The investigators analyzed a cohort of patients who underwent screening or surveillance colonoscopy at Mayo Clinic between 2021 and 2022. Patients taking any GLP-1 RA for diabetes or obesity at the time of colonoscopy were defined as "cases," and those who were prescribed a GLP-1 RA at one point but had not taken it within 3 months of colonoscopy were controls.

The Boston Bowel Preparation Scale (BBPS) was used to assess bowel preparation quality.

The study included 446 patients: 265 (59%) taking a GLP-1 RA and 181 controls (41%). Overall, the average age was 59 years, about 54% were women, and 91% were White. Among those taking a GLP-1 RA, 86% had diabetes, as did 74% of controls.

Of patients on a GLP-1 RA, 48.8% took subcutaneous semaglutide, 3.1% took oral semaglutide, 34.6% took dulaglutide, 11% took liraglutide, and very small percentages took tirzepatide or exenatide.

There were no statistically significant differences between groups at baseline except for the diabetes diagnosis.

After diabetes was controlled for, the mean BBPS was significantly higher in controls than in GLP-1 RA recipients (7.5 vs 7), and the percentage of patients with a total BBPS score < 5 was significantly higher in the GLP-1 RA group than in the control group (15.5% vs 6.6%).

In a secondary analysis of those with diabetes, the proportion of patients with a BBPS score ≤ 1 in any segment was higher in those taking a GLP-1 RA than in controls (24.9% vs 13.3%).

The proportion of patients who required a repeat colonoscopy owing to inadequate bowel prep was higher among those taking a GLP-1 RA than among controls (18.9% vs 11.1%). This corresponded to a number needed to harm of 14.

"GLP-1 RAs are increasingly used for the treatment of diabetes and obesity and have been demonstrated to reduce gastrointestinal motility," the authors write. "Our data signal that the use of these medications in this patient population may be an additional factor in suboptimal bowel preparation."

Limitations include the retrospective nature of the study, its focus on a single health system with a large majority of non-Hispanic White patients, and lack of data on diabetic complications and the use of insulin— all of which "necessitate caution in interpreting the findings," the authors write.

Research 'Evolving Rapidly'

"We will continue gathering more information on colonoscopy preparations and GLP-1 RA medication use, and whether the newer type 2 diabetes medications have a similar effect," Vargas said. "The newer and upcoming medications are double and/or triple agonists, and it remains to be determined if these have a similar effect on gastric transit times."

The recent lowering of the recommended colorectal cancer screening age for average-risk individuals to 45 combined with increasing use of GLP-1 RAs make it important to minimize repeat colonoscopies, he added.

"In the absence of specific guidance on timing of periprocedural discontinuation of GLP-1 RAs, clinicians can enhance counseling and educational efforts in this population," Vargas suggested. They can also consider interventions such as "extending bowel preparation regimens, '

issuing a clear liquid diet recommendation 48-72 hours before colonoscopy, and nurse education visits on colonoscopy preparation."

Commenting on the study, David A. Greenwald, MD, director of clinical gastroenterology and endoscopy at Mount Sinai Hospital in New York City, noted the potential confounding in a retrospective study, as well as the relatively small sample size. "Nonetheless, the findings make sense and are important to guide clinical decision-making," he told Medscape Medical News.

Gastric emptying with GLP-1 RAs can lead to retained fluid and food in the stomach, which increase the risk for aspiration at endoscopy, he said.

"We are concerned about that primarily for upper endoscopy but have seen vomiting and aspiration occur during colonoscopy in patients who have been using [these] medications," Greenwald said. It's reasonable to postulate that GLP-1 RAs could delay passage of colonoscopy preps through the gastrointestinal tract, which would affect the outcome of prep, he added.

"Research around GLP-1 agonist use and endoscopy is evolving rapidly, and we hope to have data-driven guidance soon on whether these agents need to be held in the peri-endoscopic period, and if so, for how long," Greenwald noted. "At the moment, guidance has been published but is very much driven by expert opinion and limited studies."

The study received no financial support. Vargas and Greenwald report no relevant conflicts of interest.

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