Chronic GLP1 therapy reduces postprandial IL6 in obese humans with prediabetes

Single-dose glucagon-like peptide 1 (GLP1) therapy increases postprandial plasma IL6 levels in prediabetic, obese humans. GLP1-IL6 interactions underly multiple antidiabetic effects, but these may differ after acute versus chronic therapy. This study examines postprandial effects of GLP1 after chronic therapy. Seven humans (six Black) with prediabetes and obesity completed 6 weeks of exenatide extended release therapy. Then subjects returned for pre- and post-meal measurements of plasma IL6, GLP1, glucagon, and related inflammatory markers. Weight, which was measured before and after therapy, did not change. Plasma IL6 decreased from baseline to postmeal state ( = 0.016), with decreases in free fatty acids (P < 0.001) and increases in insulin (P = 0.002), glucose (P < 0.0001), triglycerides (P = 0.0178), and glucagon (P = 0.018). Baseline GLP1 levels matched 6 weeks of therapy. The fall in postprandial plasma IL6, which contrasts with the increase after acute therapy, highlights the need for more investigation regarding the mechanisms of acute versus chronic GLP1-IL6 signaling.