Changes in hormones that regulate appetite and adipose tissue function may help explain variability in the glycemic response to glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy. A study published in the Diabetes and Metabolism Journal evaluated hormonal and metabolic changes associated with glycemic improvement during treatment with dulaglutide.

This 24-week prospective observational study enrolled 82 adults with T2DM and baseline (HbA1c levels of 7.0% or higher despite standard therapy. Participants received dulaglutide 0.75 mg once weekly, and 67 individuals completed follow-up. Assessments included abdominal computed tomography (CT), the General Food Cravings Questionnaire-Trait, and fasting levels of leptin, adiponectin, obestatin, ghrelin, and resistin at baseline and week 24. Glycemic responders were defined as achieving an HbA1c reduction of 0.5% or greater and/or an HbA1c <7.0%. Multivariable regression identified factors associated with glycemic improvement.

Dulaglutide therapy lowered HbA1c and reduced levels of leptin and adiponectin while modestly increasing obestatin. Responders demonstrated greater improvement in beta-cell function and more pronounced reductions in food-craving scores. In adjusted models, decreased leptin and increased obestatin were independently associated with HbA1c improvement. Reduced adiponectin predicted poorer glycemic outcomes. Changes in body mass index (BMI) or abdominal fat were not associated with glycemic response.

These results indicate that dulaglutide improves glycemic control through mechanisms that extend beyond weight reduction. Hormonal shifts in leptin, adiponectin, and obestatin may help identify individuals who are more likely to respond to GLP-1 RA therapy.