Plaque microstructures during metformin therapy in type 2 diabetic subjects with coronary artery disease: optical coherence tomography analysis

Background: While metformin is recommended as a first-line cardioprotective therapy for type 2 diabetic patients, whether it exerts direct effects on atherosclerotic plaque remains uncertain. The current study characterized coronary plaque microstructures in type 2 diabetic patients who received metformin. Methods: We retrospectively analyzed 409 non-culprit lipid plaques in 313 type 2 diabetic patients with coronary artery disease (CAD) by using frequency-domain optical coherence tomography (FD-OCT) imaging. FD-OCT derived plaque microstructures were compared in patients stratified according to metformin use. Results: A proportion of 38.6% of study subjects received metformin. Patients receiving metformin more likely exhibited a history of hypertension (79.3% vs. 67.1%, P=0.03) and metabolic syndrome (52.8% vs. 36.4%, P=0.01). On FD-OCT imaging, the prevalence of lipid plaque was lower in the metformin group (66.2% vs. 77.9%, P=0.03). Furthermore, the metformin group demonstrated plaques with a smaller lipid arc (median: 168.7 degrees vs. 208.5 degrees, P=0.008), shorter longitudinal length (media: 5.1 vs. 9.1 mm, P=0.04), and a lower frequency of cholesterol crystal (3.9% vs. 18.2%, P=0.01) and spotty calcification (3.9% vs. 34.8%, P=0.008). These differences remained significant after adjusting for clinical characteristics and glycemic control. However, in patients who received insulin, the favourable effect of metformin on lipid arc was not observed (insulin user: P=0.87; insulin non-user: P=0.009; P value for interaction between two groups, P=0.02). Conclusions: Metformin use was associated with a lower prevalence of vulnerable plaque features in type 2 diabetic patients with CAD, especially insulin non-user. These findings suggest the potential of metformin to exert direct plaque stabilization effects in type 2 diabetic subjects.