3-PUB: Plasma MMP-9 Concentration Is Reduced by GLP-1 Receptor Agonist Treatment in People with Type 2 Diabetes Mellitus

Introduction and Objective: Glucagon-Like Peptide 1 Receptor Agonists (GLP1RAs) reduce the risk of cardiovascular events and death in people with Type 2 Diabetes Mellitus (T2D) at high risk. Platelet hyperactivation and endothelial dysfunction contribute to elevated cardiovascular risk in T2D. Platelet factor-4, glycoprotein V, thromboxane B2, soluble P-selectin and CD40 ligand are markers of platelet activation and inflammation. Matrix metalloproteinase-9 (MMP-9), ICAM-1, VCAM-1 contribute to endothelial dysfunction and atherosclerosis. The aim of this study was to measure plasma levels of these markers of platelet activation and endothelial dysfunction, before and after 16 weeks of GLP1RA treatment in patients with T2D and to correlate this with clinical response. Methods: Plasma levels of each biomarker were measured by ELISA at baseline and 16 weeks after initiation of GLP1RA therapy in 18 people with T2D. Paired student t-tests were used to evaluate for a change in biomarker concentrations following treatment. Simple linear regression was used to evaluate the association between baseline biomarkers, and percentage change in weight and HbA1c following treatment. Results: 61% of participants were male. At baseline, mean age was 53.94 ± 2.84 years. Mean HbA1c was 67 ± 17 mmol/mol. There was no significant association between the concentration of any biomarker and clinical response, in terms of change in HbA1c or body weight. There was a 30% reduction in MMP-9 (504 ± 75 ng/mL pre-treatment to 351 ± 47 ng/mL post-treatment; SEM; p=0.047). There was no difference in concentrations of the other biomarkers following GLP1RA treatment. Conclusion: As elevated MMP-9 is implicated in atherosclerotic plaque destabilization and adverse cardiac events, reduction in MMP-9 may be a possible mechanism contributing to the cardiovascular benefits of GLP1RAs. Disclosure A. Prem Kumar: None. M. Brennan: Research Support; Current; Grifols, S.A., Novartis Pharmaceuticals Corporation. S. Sreenan: Other - Member of the organizing committee for the United Kingdom Consultant Diabetologists' forum, which is sponsored by Eli Lilly. Honorarium received; Current; Eli Lilly and Company. Other - Co-organizer of an educational event for trainee fellows in Endocrinology that is sponsored by the company. Food and lodging provided by the company; Ended; Novo Nordisk. Advisory Panel; Current; Novo Nordisk. Consultant; Ended; Eli Lilly and Company.