Calories to Satiation Predicts Patients Likely to Experience Adverse Events From GLP-1s
Patients often have anxiety about potential adverse effects, and experiencing adverse effects can affect patient adherence.
At Digestive Disease Week 2025, new findings were presented that supported machine-learning algorithms to predict patients more likely to experience gastrointestinal-related adverse events, particularly nausea, from glucagon-like peptide-1 (GLP-1) medication.1
Patients often have anxiety about potential adverse effects, and experiencing adverse effects can affect patient adherence. | Image Credit: zimmytws - stock.adobe.com
"These findings represent a meaningful advancement in how we approach obesity treatment at an individual level," Andres Acosta, MD, PhD, co-founder of Phenomix, said in a news release.1 "By identifying which patients are more likely to experience [adverse] effects before starting therapy, we can improve tolerability, support long-term adherence, and better match the right treatment to the right patient. This is a critical step toward delivering on the promise of truly personalized obesity care."
In the study, investigators aimed to determine the role of calories to satiation (CTSGRS) to identify patients at higher risk of experiencing adverse events, according to the study authors. Investigators performed a post-hoc analysis of a placebo-controlled trial for the effects of liraglutide on gastric emptying, weight loss, and other parameters for obesity. A machine learning assisted CTSGRS to find associations with adverse events in the trial.2
Of the adverse events reported, patients who had higher CTSGRS and received liraglutide were significantly more likely to develop nausea at 68% than patients with low CTSGRS at 30%. There were 2 individuals in each group of CTSGRS who withdrew from the study due to nausea, and 1 individual with high CTSGRS decreased their dosage due to nausea. Investigators reported that nausea was not associated with changes in total weight loss.2
As for other adverse events, patients with high CTSGRS were more likely to report headache and gastrointestinal-related adverse events (73%) compared with low CTSGRS (53%). However, higher CTSGRS was not associated with significant changes in gastric emptying or gastric accommodation, according to the study authors.2
"This study underscores the power of predictive tools like MyPhenome to transform how we approach obesity treatment—not just in the clinic, but in the drug development pipeline," Mark Bagnall, CEO of Phenomix Sciences, said in the news release.1 "By identifying patients at risk for [adverse] effects before treatment begins, we can match the right patient to the right therapy, increase real-world adherence, and dramatically improve clinical trial efficiency through smarter patient selection."
For liraglutide, gastrointestinal-related adverse events were most commonly reported and led to discontinuation of the medication for 6.4% of patients in a study. Nausea and vomiting occurred primarily in the first 4 to 8 weeks of initiating treatment. Patients often have anxiety about potential adverse effects, and experiencing adverse effects can affect patient adherence. Because of high plasma concentration, GLP-1s are associated with gastrointestinal adverse events.3,4
READ MORE: Diabetes Resource Center
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