Effect of Metformin on Left Ventricular Function After Acute Myocardial Infarction in Patients Without Diabetes: The GIPS-III Randomized Clinical Trial

• Published in: JAMA : the journal of the American Medical Association Vol. 311; no. 15; pp. 1526 - 1535
• Main Authors: Lexis, Chris P. H, van der Horst, Iwan C. C, Lipsic, Erik, Wieringa, Wouter G, de Boer, Rudolf A, van den Heuvel, Ad F. M, van der Werf, Hindrik W, Schurer, Remco A. J, Pundziute, Gabija, Tan, Eng S, Nieuwland, Wybe, Willemsen, Hendrik M, Dorhout, Bernard, Molmans, Barbara H. W, van der Horst-Schrivers, Anouk N. A, Wolffenbuttel, Bruce H. R, ter Horst, Gert J, van Rossum, Albert C, Tijssen, Jan G. P, Hillege, Hans L, de Smet, Bart J. G. L, van der Harst, Pim, van Veldhuisen, Dirk J
• Format: Journal Article
• Language: English
• Published: Chicago, IL American Medical Association 16.04.2014
• Subjects: Aged; Biological and medical sciences; Cardiology. Vascular system; Clinical outcomes; Coronary heart disease; Diabetes; Diabetes. Impaired glucose tolerance; Double-Blind Method; Drug therapy; Effectiveness studies; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; General aspects; Heart; Heart attacks; Humans; Hypoglycemic Agents - therapeutic use; Magnetic Resonance Imaging; Male; Medical sciences; Metformin - therapeutic use; Middle Aged; Myocardial Infarction - complications; Myocardial Infarction - drug therapy; Myocardial Infarction - physiopathology; Percutaneous Coronary Intervention; Treatment Outcome; Ventricular Dysfunction, Left - prevention & control; Ventricular Function, Left - drug effects; Endocrinopathy; Human; Myocardial infarction; Acute; Diabetes mellitus; Cardiovascular disease; Patient; Coronary heart disease; Myocardial disease; Medicine; Hypoglycemic agent; Biguanides; Gastrointestinal hormone; Clinical trial; Metformin; Left ventricle performance; Gastric inhibitory peptide
• ISSN: 0098-7484; 1538-3598; 1538-3598
• DOI: 10.1001/jama.2014.3315

IMPORTANCE Metformin treatment is associated with improved outcome after myocardial infarction in patients with diabetes. In animal experimental studies metformin preserves left ventricular function. OBJECTIVE To evaluate the effect of metformin treatment on preservation of left ventricular function in patients without diabetes presenting with ST-segment elevation myocardial infarction (STEMI). DESIGN, SETTING, AND PARTICIPANTS Double-blind, placebo-controlled study conducted among 380 patients who underwent primary percutaneous coronary intervention (PCI) for STEMI at the University Medical Center Groningen, the Netherlands, between January 1, 2011, and May 26, 2013. INTERVENTIONS Metformin hydrochloride (500 mg) (n = 191) or placebo (n = 189) twice daily for 4 months. MAIN OUTCOMES AND MEASURES The primary efficacy measure was left ventricular ejection fraction (LVEF) after 4 months, assessed by magnetic resonance imaging. A secondary efficacy measure was the N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration after 4 months. The incidence of major adverse cardiac events (MACE; the combined end point of death, reinfarction, or target-lesion revascularization) was recorded until 4 months as a secondary efficacy measure. RESULTS At 4 months, all patients were alive and none were lost to follow-up. LVEF was 53.1% (95% CI, 51.6%-54.6%) in the metformin group (n = 135), compared with 54.8% (95% CI, 53.5%-56.1%) (P = .10) in the placebo group (n = 136). NT-proBNP concentration was 167 ng/L in the metformin group (interquartile range [IQR], 65-393 ng/L) and 167 ng/L in the placebo group (IQR, 74-383 ng/L) (P = .66). MACE were observed in 6 patients (3.1%) in the metformin group and in 2 patients (1.1%) in the placebo group (P = .16). Creatinine concentration (79 µmol/L [IQR, 70-87 µmol/L] vs 79 µmol/L [IQR, 72-89 µmol/L], P = .61) and glycated hemoglobin (5.9% [IQR, 5.6%-6.1%] vs 5.9% [IQR, 5.7%-6.1%], P = .15) were not significantly different between both groups. No cases of lactic acidosis were observed. CONCLUSIONS AND RELEVANCE Among patients without diabetes presenting with STEMI and undergoing primary PCI, the use of metformin compared with placebo did not result in improved LVEF after 4 months. The present findings do not support the use of metformin in this setting. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01217307.