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. 2022 Feb;12(1):77-87.
doi: 10.21037/cdt-21-346.

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

Yu Kataoka  1 , Stephen J Nicholls  2 , Jordan Andrews  3 , Kiyoko Uno  4 , Samir R Kapadia  5 , E Murat Tuzcu  5 , Steven E Nissen  5 , Rishi Puri  5   6
Affiliations

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

Yu Kataoka et al. Cardiovasc Diagn Ther. 2022 Feb.

Abstract

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° vs. 208.5°, 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.

Keywords: Diabetes mellitus; coronary artery disease (CAD); optical coherence tomography (OCT); plaque.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-21-346/coif). YK has received research support from Nipro and Abbott, and honoraria from Nipro, Abbott, Kowa, Amgen, Sanofi, Astellas, Takeda and Daiichi-Sankyo. SJN is a consultant for AstraZeneca, Amgen, Boehringer Ingelheim, CSL Behring, Merck, Takeda, Novartis, Pfizer, Sanofi-Regeneron, Eli Lilly and Roche and has received research support from AstraZeneca, Amgen, Cerenis, Novartis, Resverlogix, Eli Lilly, InfraReDx, Anthera, Roche, Sanofi-Regeneron and Lipid Sciences. KU was an employee of Sanofi before joining this study. SEN has received research support to perform clinical trials through the Cleveland Clinic Coordinating Center for Clinical Research from Pfizer, AstraZeneca, Novartis, Roche, Daiichi-Sankyo, Takeda, Sanofi-Aventis, Resverlogix, and Eli Lilly; and is a consultant/advisor for many pharmaceutical companies but requires them to donate all honoraria or consulting fees directly to charity so that he receives neither income nor a tax deduction. YK and SJN serve as unpaid editorial board members of Cardiovascular Diagnosis and Therapy from Jul 2019 to Jun 2021. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Representative cases. (A) A 65-year-old gentleman received percutaneous coronary intervention (PCI) at the middle segment of hid left anterior descending artery (white dotted line). He has not taken metformin prior to PCI. optical coherence tomography (OCT) imaging at non-culprit segment (white arrow head) demonstrated a large lipid-rich plaque (L) containing cholesterol crystal (white arrow). (B) A 50-year gentleman was hospitalized due to anginal chest pain. Stent implantation was conducted at the middle segment of hid left anterior descending artery (white dotted line). He was treated by metformin. On OCT imaging, non-culprit segment (white arrow head) exhibited a small lipid plaque (L) without any cholesterol crystal.
See this image and copyright information in PMC

References

    1. American Diabetes Association . 8. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2018. Diabetes Care 2018;41:S73-85. 10.2337/dc18-S008 - DOI - PubMed
    1. Authors/Task Force Members ; Rydén L, Grant PJ, et al. ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD). Eur Heart J 2013;34:3035-87. 10.1093/eurheartj/eht108 - DOI - PubMed
    1. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:854-65. 10.1016/S0140-6736(98)07037-8 - DOI - PubMed
    1. Cameron AR, Morrison VL, Levin D, et al. Anti-Inflammatory Effects of Metformin Irrespective of Diabetes Status. Circ Res 2016;119:652-65. 10.1161/CIRCRESAHA.116.308445 - DOI - PMC - PubMed
    1. Ramachandran S, Anandan V, Kutty VR, et al. Metformin attenuates effects of cyclophilin A on macrophages, reduces lipid uptake and secretion of cytokines by repressing decreased AMPK activity. Clin Sci (Lond) 2018;132:719-38. 10.1042/CS20171523 - DOI - PubMed