A prospective cohort study published in Clinical Nutrition reports that elevated plasma glucagon-like peptide-1 (GLP-1) was associated with enteral feeding intolerance in patients with traumatic brain injury. The authors describe the findings as hypothesis-generating rather than conclusive, which is the right call and worth noting given how rarely GLP-1 papers arrive that modest.

GLP-1 is a gut hormone the researchers note is involved in satiety signaling, and it is the same pathway targeted by drugs such as semaglutide (sold as Ozempic and Wegovy). Enteral feeding is nutrition delivered by tube directly into the gut, and the study team defines intolerance as a patient receiving less than 70 percent of their caloric goal.

Who was in the cohort

The researchers enrolled 109 adults aged 18 to 80 with traumatic brain injury at a tertiary neuro-ICU, using a standardized feeding strategy that targeted 25 kcal per kg per day and was adjusted according to tolerance. Blood was sampled across four post-injury day windows covering days 1 to 14.

Measurements included GLP-1, insulin, glucose and glial fibrillary acidic protein, a marker the team associates with brain injury severity. That last inclusion is what makes the paper more interesting than a straightforward nutrition audit.

Key results

Of the 109 patients, 50 met the definition of feeding intolerance and 59 did not. Insulin and glucose did not differ between the two groups, while GLP-1 was higher in the intolerance group.

GLP-1 also increased with injury severity and was greatest in patients with a Glasgow Coma Scale score of 3 to 5 compared with 6 to 12. It correlated with glial fibrillary acidic protein over the 14 days, while intestinal permeability markers did not differ between groups.

In multivariable models, GLP-1 measured on post-injury days 8 to 10, IL-6 over the same window, insulin on days 1 to 3 and admission SOFA score were each independently associated with feeding intolerance. Combining early insulin and SOFA score gave an area under the curve of 0.786, with a reported specificity of 71.4 percent and sensitivity of 75 percent.

Central GLP-1 resistance

The team proposes that disrupted central GLP-1 signaling may reduce satiety input and produce what they term central GLP-1 resistance, with GLP-1 accumulating in plasma as a secondary effect. On that reading, higher circulating GLP-1 may indicate the resistance rather than cause the intolerance directly.

Limitations

The authors state plainly that the findings are hypothesis-generating and describe an association, not a demonstrated mechanism. The cohort was a single tertiary neuro-ICU with 109 patients, followed for 14 days, and the paper does not report an external validation of the risk model.

A marker, not yet a mechanism

The conclusion is that elevated plasma GLP-1 is associated with enteral feeding intolerance after traumatic brain injury and may serve as a pragmatic predictor. Whether altered GLP-1 signaling contributes to that intolerance, the authors say, remains unresolved.