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Metformin is the recommended first line therapy for type 2 diabetes with a benefit of possibly lowering cardiovascular risk.1 Previous observational studies have shown that patients with diabetes have a lower risk of experiencing a second myocardial infarction while concurrently being treated with metformin.2 Experimental studies in non-diabetic rat models have shown a relative 52% improvement in left ventricular ejection fraction (LVEF) post-MI with metformin therapy compared to placebo.3 Thus, these findings have generated attention for its use in patients without diabetes. Additionally, up to 50% of patients presenting with an ST-segment elevation myocardial infarction (STEMI) can develop left ventricular dysfunction, and 20% to 40% can develop heart failure making this population of particular interest to study metformin’s potential cardiovascular benefits.4,5

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The investigators in the GIPS-III trial examined the effects of metformin on left ventricular function in post-MI, nondiabetic patients. The comparison of metformin to placebo and its effect on left ventricular function, measured by the LVEF, had not previously been studied in a prospective clinical trial in this population. Patients without diabetes presenting with a STEMI who received a percutaneous coronary intervention with the type of intervention decided upon by the operator were eligible for inclusion. Patients were excluded if they had a prior MI, known diabetes, need for coronary bypass artery grafting, or severe renal function. After the PCI, patients were randomized to receive metformin 500mg twice daily or placebo twice daily, which was blinded to both patients and investigators. The first dose was administered as soon as possible (ideally within 3 hours of PCI) and treatment continued for 4 months. Patients received an MRI to measure LVEF as the primary outcome measure. The principal secondary efficacy measure was N-terminal pro brain natriuretic peptide (NT-proBNP) concentrations due to its clinical indication for heart failure. Other secondary outcome measures included the combined end point major adverse cardiac events, also known as MACE (cardiovascular death, recurrent MI, and target-lesion revascularization), creatinine, glucose and HbA1C concentrations.6  Patients followed up at an outpatient clinic at 2 weeks, 7 weeks, and 4 months after discharge to assess adherence.  At the 4 month follow-up the primary and secondary outcome measures were assessed.

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A total of 380 patients were enrolled in the study with 189 patients receiving placebo and 191 patients receiving metformin.  Baseline characteristics were similar between both groups. MRI results revealed no significant difference in LVEF after 4 months between the metformin group (53.1% [95% CI, 51.6-54.6%]) and placebo group (54.8% [95% CI, 53.5%-56.1%] P=.10). Concentration of NT-proBNP at the 4 month follow-up also did not differ between groups with a median of 167ng/L (IQR 65-393 ng/L) in the metformin group and 167ng/L (IQR 74-375 ng/L) in the placebo group (P=.66). No significant differences were observed in the individual end points and the combined MACE end points with 3% in the metformin group versus 1% in the placebo group ...

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