TOPLINE

Patients with obesity beginning GLP-1 therapy had a higher prevalence of constipation than nonusers. Those without prior constipation showed a nearly 50% higher relative risk after starting treatment; however, the actual incidence of new-onset constipation remained low, affecting fewer than 4% within a year.

METHODOLOGY

• Constipation is a common adverse effect of GLP-1 and a frequent reason for treatment discontinuation; however, it isn’t clear if the drugs increase incident constipation risk.
• Researchers used data from the All of Us Research Program and analyzed 111,545 patients with obesity. GLP-1 exposure was defined as the first recorded prescription of semaglutide, tirzepatide, or liraglutide, with comparative analysis including other weight-loss drugs such as bupropion-naltrexone and phentermine-topiramate. A cross-sectional analysis was conducted to assess constipation prevalence during the study period, which included 11,656 GLP-1 users, 917 bupropion-naltrexone users, 728 phentermine-topiramate users, and 91,305 nonusers. Patients with prior constipation were included in this analysis.
• A longitudinal analysis evaluated new-onset constipation within 1 year after initiating GLP-1s. Patients with a prior history of constipation before the initiation of the drug were excluded, and follow-up was continued until the first event of constipation or 1 year after starting the drug.
• For the longitudinal analysis, 8188 GLP-1 users (6080 on semaglutide, 3126 on liraglutide, and 940 on tirzepatide) were matched with GLP-A nonusers; similarly, 495 bupropion-naltrexone and 368 phentermine-topiramate users were each matched with those who did not receive these regimens.

TAKEAWAY

• In this cross-sectional analysis, constipation prevalence was higher among GLP-1 users than among nonusers (31.6% vs 26.8%; P < .001); rates were similarly higher among users of bupropion-naltrexone (30.1%) and phentermine-topiramate (30.4%) than among nonusers (P < .05).
• In the longitudinal analysis, the 1-year incidence of constipation among GLP-1 users was 3.34 per 100 person-years, with a mean time to event of 141 days; incidence rates were 2.90, 4.16, and 1.81 per 100 person-years for semaglutide, liraglutide, and tirzepatide, respectively. Incidence rates for other weight-loss medications were similar or higher, though only GLP-1s showed a significant increase.
• GLP-1 users had a higher risk for new-onset constipation than nonusers (hazard ratio [HR], 1.49); similar findings were observed among users of semaglutide (HR, 1.31), liraglutide (HR, 1.44), and tirzepatide (HR, 2.83; P < .05 for all). No significant risk was observed with other weight-loss medications.

IN PRACTICE

“[The study] findings suggest that although constipation merits monitoring as a potential adverse effect in patients, particularly among patients with greater comorbidity burden, concerns about [new-onset] constipation should likely not be considered a major deterrent to initiating GLP-1 therapy,” the authors of the study wrote. “Nevertheless, the absolute risk of developing new-onset constipation after starting these medications is quite low and may provide reassurance to patients and clinicians.”

SOURCE

The study was led by Madeleine Chang, Harvard University, Cambridge, Massachusetts. It was published online as a research letter in Clinical Gastroenterology and Hepatology.

LIMITATIONS

The study did not assess constipation severity using standardized measures. It did not capture patients with preexisting constipation who may have experienced worsening symptoms after starting a GLP-1. Mild constipation, or cases treated with over-the-counter remedies, may have gone uncounted.

DISCLOSURES

No funding information was explicitly mentioned for the study. One author disclosed receiving research support and serving as a consultant to various biopharmaceutical, medical device, and digital health companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.