Mazdutide trial to assess coronary plaque progression in overweight/obese patients with atherosclerosis

Coronary atherosclerosis is a leading cause of cardiovascular disease, often exacerbated by overweight and obesity. Current treatments focus on risk factor management, but direct plaque regression remains a significant challenge. Dual GLP-1/GCG receptor agonists like mazdutide have shown substantial weight loss benefits, and their potential to modulate metabolic pathways involved in atherosclerosis progression, beyond just weight reduction, warrants investigation. This trial addresses the gap in understanding how these novel agents might directly impact coronary plaque.

This multicenter, randomized, double-blind, placebo-controlled trial investigates mazdutide 9 mg on coronary plaque progression in patients with coronary atherosclerosis and overweight or obesity. The primary endpoint is the change in total non-calcified plaque volume (NCPV) from baseline to week 52, assessed by coronary computed tomography angiography (CCTA). Secondary endpoints include changes in pericoronary adipose tissue inflammation (FAI), plaque composition, metabolic parameters, inflammatory biomarkers, and clinical outcomes. A substudy will also utilize 18F-NAF PET/CT imaging.