Exenatide once weekly falls short of reducing carotid plaque progression in T2D

The long-acting glucagon-like peptide 1 receptor agonist (GLP-1RA) exenatide once weekly helps improve glycaemic control but does little to modify carotid plaque volume or composition in patients with type 2 diabetes (T2D), according to the results of a trial.

A total of 163 T2D patients were randomized to receive exenatide once weekly (n=109) or placebo (n=54) for 18 months. Efficacy was evaluated based on changes in carotid plaque volume and composition at 9 and 18 months using a multicontrast 3 Tesla magnetic resonance imaging. Other outcomes assessed were fasting and post-high-fat meal plasma glucose and lipids, and endothelial function responses at 3, 9, and 18 months.

Eighteen-month data revealed similar changes in plaque volume in the exenatide and placebo groups (0.3 percent vs −2.2 percent, respectively; p=0.4).

However, the study drug produced a significant reduction in haemoglobin A1c (HbA1c; estimated difference vs placebo, 0.55 percent; p=0.0007) and fasting and postmeal plasma glucose (estimated differences, 19 mg/dL; p=0.0002 and 25 mg/dL; p<0.0001, respectively).

The change in plaque volume with exenatide correlated with changes in HbA1c (p=0.0004), body weight (p=0.007), and overall plasma glucose (p=0.007). There were no significant between-group differences in plaque composition changes, body weight, blood pressure, fasting and postmeal plasma triglycerides, and endothelial function between the groups.

The findings raise the possibility that short-term anti-atherosclerotic effects may not play a central role in the cardiovascular benefits of GLP-1RAs.