Written by Babatunde Carew
Spoon Feed
Twice-weekly glepaglutide (a long acting GLP-2 analog) significantly reduced parenteral support requirements in patients with short bowel syndrome and intestinal failure, with some achieving enteral autonomy.
Gut reaction – glepaglutide cuts parenteral support
Short bowel syndrome (SBS) is the leading cause of intestinal failure (IF), where insufficient bowel length impairs nutrient and fluid absorption, necessitating parenteral support (PS). GLP-2 analogs have been shown to improve outcomes by enhancing intestinal adaptation and reducing PS dependence. This phase 3, randomized, placebo-controlled trial evaluated whether glepaglutide, a long-acting GLP‑2 analog, reduces PS requirements in patients with SBS and IF. In 106 patients over 24 weeks, twice-weekly dosing significantly reduced PS (–5.13 L/wk vs –2.85 L/wk; difference –2.28 L/wk, P=0.0039), with 65.7% achieving ≥20% reduction and 14% stopping PS. One area of concern was severe adverse effects (SAE), such as device-related sepsis, vascular device infection, catheter site necrosis, or stoma site hemorrhage. Patients treated with twice a week glepaglutide had an incidence of 28.6% (33% were infection-related), once a week glepaglutide had an incidence of 11.4% (55% infection-related), and placebo had an incidence of 5.6% (100% infection-related). Stoma site hemorrhage only occurred in twice weekly glepaglutide injections. Limitations include small sample size and treatment duration.
How does this change my practice?
As a primary care physician, I do not treat many patients with SBS. However, this is promising and would lead me to advocate for the use of glepaglutide for my own patients. It had reasonable tolerability, and most frequent adverse events were mild. I would also counsel my patients on the risks of infection, stoma hemorrhage, and follow them carefully.
Source
Glepaglutide, a Long-Acting Glucagon-like Peptide-2 Analogue, Reduces Parenteral Support in Patients With Short Bowel Syndrome: A Phase 3 Randomized Controlled Trial. Gastroenterology. 2024 Dec 19:S0016-5085(24)05787-1. doi: 10.1053/j.gastro.2024.11.023. Epub ahead of print. PMID: 39708985
