Weight loss mediates improvement in proinsulin processing during GLP-1 receptor agonist treatment

To observe the effect of glucagon-like peptide-1 receptor agonists (GLP-1RA) combined with metformin and metformin monotherapy on proinsulin changes in patients with obesity following weight loss. To explore whether the changes of proinsulin were related to GLP-1RA or secondary to weight reduction.

100 adults with obesity (BMI ≥ 28 kg/m²) were randomized to 24-week treatment with liraglutide plus metformin (GLP-1RA group, n = 50) or metformin alone (1500 mg/day; control group, n = 50). All participants received standardized lifestyle interventions, including a 500 kcal/day energy-deficit diet and 150 min/week moderate intensity aerobic exercise. Visceral fat area (VFA) and body fat percentage (PBF) were measured using multifrequency bioelectrical impedance analysis (InBody770; Biospace Inc., Korea). Proinsulin levels were quantified via a chemiluminescent enzyme-linked immunosorbent assay (Human Proinsulin ELISA Kit, BayBio). Multiple regression analyses were applied to adjust for age, gender, baseline BMI, and treatment allocation, isolating weight loss effects from direct drug actions.

The weight, blood lipids and glucose metabolism indexes of two groups were significantly improved, and the effects were more significant in the GLP-1RA group. Correlation analysis showed that proinsulin change was positively correlated with body weight change and VFA change, which persisted after adjusting for confounding factors such as age, gender, baseline body mass index (BMI), and GLP-1RA medication.

GLP-1RA demonstrate superior weight loss effects and improvements in lipid and glucose metabolism in patients with obesity. However, the reduction in proinsulin levels is primarily attributed to the magnitude of weight loss itself, independent of GLP-1RA use.