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Gastrointestinal adverse events mild after therapy with GLP-1 receptor agonists

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April 27, 2017

Patients with type 2 diabetes experienced gastrointestinal events less frequently when treated with a once-weekly dose of the glucagon-like peptide-1 receptor agonist exenatide than a twice-daily dose of exenatide or liraglutide, according to findings published in Diabetes, Obesity and Metabolism.

“GLP-1 [receptor agonists] have been shown to reduce HbA1c and body weight, with low intrinsic risk of hypoglycemia,” the researchers wrote. “One potential [adverse event] associated with these agents is an increase in gastrointestinal events that is transient in most cases. As such, understanding the specific gastrointestinal [adverse event] profile and how it varies across the GLP-1 [receptor agonist] class is of interest for patients and physicians and may be useful in guiding therapy.”

Chris K. Rayner, MBBS, PhD, in the discipline of medicine, University of Adelaide in Australia, and colleagues evaluated data from a pooled analysis of the DURATION-1, DURATION-5 and NCT00917267 studies comparing exenatide once weekly (n = 617; Bydureon, AstraZeneca) with exenatide twice daily (n = 606; Byetta, AstraZeneca) and a separate analysis of DURATION-6, which compared exenatide once weekly (n = 461) with liraglutide once daily (n = 450; Victoza, Novo Nordisk), to determine prevalence of gastrointestinal adverse events.

Fewer participants treated with exenatide once weekly experienced gastrointestinal adverse events compared with those treated with exenatide twice daily (34% vs. 45%; P < .0001) or with liraglutide (25% vs. 41%; P < .0001). Similarly, fewer participants treated with exenatide once weekly reported upper gastrointestinal adverse events compared with participants treated with exenatide twice daily (P < .0001) or liraglutide (P < .001). No difference was found between participants treated with either exenatide dose for lower gastrointestinal adverse events, whereas participants treated with liraglutide experienced diarrhea more often than participants treated with exenatide once weekly (P < .001).

Women reported more gastrointestinal adverse events compared with men in the pooled analysis for exenatide once weekly (P < .05) and exenatide twice daily (P < .001) and in the DURATION-6 analysis for exenatide once weekly (P < .01) and liraglutide (P < .01).

All gastrointestinal adverse events were reported as mild.

All treatments at week 26 resulted in reductions from baseline HbA1c and body weight (all P > .05 vs. baseline).

“The present study provides detailed information on the gastrointestinal tolerability of three GLP-1 [receptor agonists] based on patient-level data from the exenatide once-weekly clinical trial program,” the researchers wrote. “Gastrointestinal [adverse events] were usually mild and transient and particularly affected the upper gastrointestinal tract, and occurred more frequently with exenatide twice daily and liraglutide than with exenatide once weekly. These insights inform physician and patient expectations of potential experiences when initiating GLP-1 [receptor agonist] therapy.” – by Amber Cox

Disclosure: Rayner reports receiving research funding from AstraZeneca, Merck Sharp & Dohme, Novartis and Sanofi. The study was funded in part by AstraZeneca. Please see the full study for a list of all other authors’ relevant financial disclosures.

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