Colonoscopy is a common procedure. In 2013 an estimated 14 million colonoscopies were performed in the USA, with 80% performed for colorectal cancer screening [1]. The effectiveness, accuracy, and safety of colonoscopy is incumbent on a variety of factors codified by professional organizations as key performance indicators. It is recommended that adequate bowel preparation, one of the most important quality metrics, is attained in ≥90% of patients, and this is endorsed in both the European and US guidelines [2] [3]. Inadequate bowel preparation (IBP) has been demonstrated in 15 %–35 % of colonoscopies and varies by the medical setting and patient population, ultimately negatively impacting other quality metrics including the adenoma detection and cecal intubation rates, while lengthening the procedure time, reducing surveillance intervals, and increasing costs. A few of the known factors associated with IBP include diabetes, obesity, gastroparesis and other motility disorders, constipation, and medications such as anticholinergics, angiotensin converting enzyme inhibitors, calcium channel and angiotensin receptor blockers, tricyclic antidepressants, and opiates, to name a few.

The use of glucagon-like peptide-1 receptor agonists (GLP-1RAs), approved over 20 years ago for the management of type 2 diabetes mellitus and since 2014 for chronic weight management in obesity, is increasing. Recent prescribing trends in the USA for both GLP-1RAs and dual GLP-1RA/gastric inhibitory polypeptide medications report there were over 1 million patient prescriptions between 2018 and 2023, with 4213888 total prescriptions during that time [4].

Gastrointestinal (GI) symptoms including nausea, vomiting, diarrhea, and constipation are among the commonest adverse effects of GLP-1RAs. GI dysmotility, particularly gastroparesis, has been increasingly recognized and reported to impact upper GI endoscopic procedure efficacy and patient safety. A recent meta-analysis of 13 studies involving 84065 patients observed a significant association between GLP-1RA use and higher rates of residual gastric contents, and aborted and repeated procedures, but not of aspiration, compared with nonusers [5].

To date, evidence suggesting adverse impacts of GLP-1RA use on colonoscopy cleansing has been inconclusive. Prior to the study by Abu-Freha et al. [6], the available information on the impact of GLP-1RAs on bowel cleansing had come from three retrospective single-center case–control studies and, to put the Abu-Freha study into perspective, these included a total of 1061 patients.

A US study of 446 diabetic (n = 362) and nondiabetic (n = 84) patients showed a lower Boston Bowel Preparation Scale (BBPS) score in GLP-1RA users than in nonusers (7.0 [SD 1.9] vs. 7.5 [SD 2.4]; P = 0.046) when controlling for diabetes [7]. The need for repeat colonoscopy because of poor bowel preparation was higher in users than nonusers at 18.9% vs. 11.1%, respectively (P = 0.04).

Two studies in diabetics found no significant worsening of bowel preparation quality with GLP-1RA use. In a study in 360 Chinese patients, IBP was observed in 17.5% of patients on liraglutide, 20.5% of patients on the dipeptidyl peptidase-4 inhibitor sitagliptin, and 21.7% of the control diabetic group [8]. In subgroup analysis, diabetic peripheral neuropathy had a profound impact on bowel preparation, particularly in the liraglutide group compared with the sitagliptin users (61.3% vs. 32.1%; P = 0.02) and the control group (61.3% vs. 32.8%; P = 0.03). The third study, which excluded diabetics with known autonomic neuropathy, observed fewer than 10% had unsatisfactory bowel preparation, with no significant difference between the 126 patients on a GLP-1RA and the 129 patients not exposed (7.95% vs. 7.75%, respectively) [9].

The study by Abu-Freha et al. [6], the largest to assess bowel preparation adequacy, used data from seven centers in Israel including 4876 patients treated with GLP-1RA and 4876 controls without GLP-1RA exposure who were undergoing outpatient colonoscopy, with a more rigorous design than the previous studies [9]. Their study included nondiabetic and diabetic cases, and controls who were propensity score matched for co-morbidities, age, sex, diabetes, and obesity. IBP was defined as poor or inadequate on the Aronchik scale or <5 on the BPPS. Overall, a significantly higher rate of IBP was found among GLP-1RA users (10%) compared with the non-GLP-1RA group (4%; P < 0.001). On subgroup analysis of the diabetic patients, IBP was higher for users of GLP-1RAs at 12% compared with 5% among nonexposed diabetic patients (P < 0.001). Nondiabetic patients treated with a GLP-1RA had an 8.1% rate of IBP, compared with a rate of 3.1% among nondiabetic patients without GLP-1RA exposure (P < 0.001). Among those not using a GLP-1RA, higher rates of IBP were observed in patients with diabetes (5%) compared with nondiabetics (3.1%; P = 0.001). On multivariate analysis, significant associations with IBP were found for GLP-1RA use (odds ratio [OR] 2.68, 95%CI 2.26–3.18) and the presence of diabetes (OR 1.43, 95%CI 1.21–1.68).

This study demonstrates that GLP-1RA use at least doubles the proportion of patients with an IBP, and diabetes is reinforced as an independent factor for IBP. The overall rate of IBP in this study is lower than has been reported in previous studies, possibly owing to selection bias. Future studies must include diverse populations, including patients with co-morbidities or medications associated with IBP to understand the true IBP rates. The impact of dose, route of administration, dosing interval, and duration of GLP-1RA treatment on IBP needs to be understood. Abu-Freha et al. report that the highest rates of IBP were found in users of dulaglutide at 12.0%, followed by semaglutide at 10.1%, and liraglutide at 8.5%, yet there is a paucity of knowledge on the impact of different GLP-1RAs or dual GLP-1RA/gastric inhibitory polypeptide medications on IBP. The duration of the diabetes, adequacy of blood sugar control, presence of diabetic neuropathy, and history of constipation or poor bowel preparation should be included as additional variables for investigation. Because nausea and vomiting may influence the completion of laxative preparation, the amount of bowel preparation ingested for bowel cleansing is also required information. The time of day of the colonoscopy and whether an esophagogastroduodenoscopy was performed prior to the colonoscopy (which may impact the preprocedural fasting time) should also be reported.

In summary, it appears IBP is higher in GLP-1RA users regardless of the presence of diabetes and this may warrant additional preparation recommendations. Studies that overcome the previously mentioned limitations are needed and a clinical risk score to personalize the approach to bowel preparation adequacy in GLP-1RA users is desirable.

Article published online:
22 November 2024

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