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Effects of Metformin Therapy on Coronary Endothelial Dysfunction in Patients With Prediabetes With Stable Angina and Nonobstructive Coronary Artery Stenosis: The CODYCE Multicenter Prospective Study.

  • Sardu, Celestino1
  • Paolisso, Pasquale2
  • Sacra, Cosimo3
  • Mauro, Ciro4
  • Minicucci, Fabio4
  • Portoghese, Michele5
  • Rizzo, Maria Rosaria2
  • Barbieri, Michelangela2
  • Sasso, Ferdinando Carlo2
  • D'Onofrio, Nunzia6
  • Balestrieri, Maria Luisa6
  • Calabrò, Paolo7
  • Paolisso, Giuseppe2
  • Marfella, Raffaele2
  • 1 Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania "Luigi Vanvitelli," Naples, Italy [email protected] , (Italy)
  • 2 Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania "Luigi Vanvitelli," Naples, Italy. , (Italy)
  • 3 Department of Cardiovascular Diseases, John Paul II Research and Care Foundation, Campobasso, Italy. , (Italy)
  • 4 Department of Cardiovascular Diseases, Antonio Cardarelli Hospital, Naples, Italy. , (Italy)
  • 5 UOC Division of Cardiovascular Surgery, Sassari Hospital, Sassari, Italy. , (Italy)
  • 6 Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples, Italy. , (Italy)
  • 7 Division of Clinical Cardiology, AORN Sant'Anna e San Sebastiano, Caserta, Italy. , (Italy)
Published Article
Diabetes care
Publication Date
Oct 01, 2019
DOI: 10.2337/dc18-2356
PMID: 30796109


To evaluate the effect of metformin therapy on coronary endothelial function and major adverse cardiac events (MACE) in patients with prediabetes with stable angina and nonobstructive coronary stenosis (NOCS). Metformin therapy may be needed to reduce coronary heart disease risk in patients with prediabetes. A total of 258 propensity score-matched (PSM) patients with stable angina undergoing coronary angiography were enrolled in the study. Data from 86 PSM subjects with normoglycemia (NG), 86 PSM subjects with prediabetes (pre-DM), and 86 PSM subjects with prediabetes treated with metformin (pre-DM metformin) were analyzed. During coronary angiography, NOCS was categorized by luminal stenosis <40% and fractional flow reserve >0.80. In addition, we assessed the endothelial function, measuring coronary artery diameter of left anterior descending coronary (LAD) at baseline and after the infusion of acetylcholine, by means of an intracoronary Doppler guide wire. MACE, as cardiac death, myocardial infarction, and heart failure, was evaluated at 24 months of follow-up. At baseline, NG patients had a lower percentage of LAD endothelial dysfunction compared with pre-DM patients (P < 0.05). The pre-DM patients had a higher percentage of endothelial LAD dysfunction as compared with the pre-DM metformin patients (P < 0.05). At the 24th month of follow-up, MACE was higher in pre-DM versus NG (P < 0.05). In pre-DM metformin patients, MACE was lower compared with pre-DM patients (P < 0.05). Metformin therapy may reduce the high risk of cardiovascular events in pre-DM patients by reducing coronary endothelial dysfunction. © 2019 by the American Diabetes Association.

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