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• W3100556329 abstract "Background Metabolic dysfunction is highly prevalent in pulmonary arterial hypertension (PAH) and likely contributes to both pulmonary vascular disease and right ventricular (RV) failure in part because of increased oxidant stress. Currently, there is no cure for PAH and human studies of metabolic interventions, generally well tolerated in other diseases, are limited in PAH. Metformin is a commonly used oral antidiabetic that decreases gluconeogenesis, increases fatty acid oxidation, and reduces oxidant stress and thus may be relevant to PAH. Methods and Results We performed a single-center, open-label 8-week phase II trial of up to 2 g/day of metformin in patients with idiopathic or heritable PAH with the co-primary end points of safety, including development of lactic acidosis and study withdrawal, and plasma oxidant stress markers. Exploratory end points included RV function via echocardiography, plasma metabolomic analysis performed before and after metformin therapy, and RV triglyceride content by magnetic resonance spectroscopy in a subset of 9 patients. We enrolled 20 patients; 19/20 reached the target dose and all completed the study protocol. There was no clinically significant lactic acidosis or change in oxidant stress markers. Metformin did not change 6-minute walk distance but did significantly improve RV fractional area change (23±8% to 26±6%, P=0.02), though other echocardiographic parameters were unchanged. RV triglyceride content decreased in 8/9 patients (3.2±1.8% to 1.6±1.4%, P=0.015). In an exploratory metabolomic analysis, plasma metabolomic correlates of ≥50% reduction in RV lipid included dihydroxybutyrate, acetylputrescine, hydroxystearate, and glucuronate (P<0.05 for all). In the entire cohort, lipid metabolites were among the most changed by metformin. Conclusions Metformin therapy was safe and well tolerated in patients with PAH in this single-arm, open-label phase II study. Exploratory analyses suggest that metformin may be associated with improved RV fractional area change and, in a subset of patients, reduced RV triglyceride content that correlated with altered lipid and glucose metabolism markers. Registration URL: http://www.clinicaltrials.gov; Unique identifier: NCT01884051." @default.
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• W3100556329 date "2020-11-17" @default.
• W3100556329 modified "2023-10-16" @default.
• W3100556329 title "Mechanistic Phase II Clinical Trial of Metformin in Pulmonary Arterial Hypertension" @default.
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• W3100556329 cites W1966590827 @default.
• W3100556329 cites W1971915589 @default.
• W3100556329 cites W1974403293 @default.
• W3100556329 cites W1978214583 @default.
• W3100556329 cites W1987015387 @default.
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• W3100556329 cites W1990875061 @default.
• W3100556329 cites W1995069275 @default.
• W3100556329 cites W1997759488 @default.
• W3100556329 cites W1998562191 @default.
• W3100556329 cites W2001510319 @default.
• W3100556329 cites W2005097808 @default.
• W3100556329 cites W2005703091 @default.
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• W3100556329 cites W2033643811 @default.
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• W3100556329 cites W2087701915 @default.
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• W3100556329 cites W2095314259 @default.
• W3100556329 cites W2130661187 @default.
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• W3100556329 doi "https://doi.org/10.1161/jaha.120.018349" @default.
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