Journal: American Journal of Respiratory Cell and Molecular Biology

Article Title: Activation of the Metabolic Master Regulator PPARγ: A Potential PIOneering Therapy for Pulmonary Arterial Hypertension

doi: 10.1165/rcmb.2019-0226PS

Figure Lengend Snippet: Clinical Trials

Article Snippet: van der Meer et al. , 2009 ( 43 ) PIRAMID Pioglitazone vs. metformin • 15 mg once daily • Titrated to 30 mg once daily after 2 wk , Evaluate pioglitazone vs. metformin effects on myocardial function, dimensions, and perfusion in association with cardiac glucose, fatty acid metabolism, triglycerides, and high-energy phosphate metabolism 24-wk prospective, randomized, double-blind, double-dummy with active comparator, two-center parallel-group intervention , 78 enrolled 34 pioglitazone 37 metformin , Inclusion • Men aged 45–65 yr with uncomplicated T2DM without ischemic heart disease • Glycohemoglobin concentration 6.5–8.5% at screening, BMI of 25–32 kg/m 2 , and blood pressure not >150/85 mm Hg (with or without antihypertensives) Major exclusion • Cardiovascular disease • Liver disease • DM-related complications , Primary outcome • Change baseline to follow-up at 24 wk in diastolic function Results • Pioglitazone ↑ in indices of diastolic function, ↑ LVEDP, and improved LV compliance • Pioglitazone ↑ stroke volume • Metformin did not impact diastolic parameters , Secondary outcomes • Difference in cardiac dimensions, systolic function, blood pressure, myocardial metabolism, perfusion variables, hepatic and myocardial triglycerides, plasma lipids, BMI, glycohemoglobin, and whole-body insulin sensitivity Results • Pioglitazone ↑ HDL and weight gain and ↓ hepatic triglycerides • No difference between groups on ↑ insulin sensitivity, systolic BP • No change in myocardial fatty acid uptake, but metformin ↓ myocardial fatty acid oxidation • Additional metabolic effects: ↓ plasma lactate in pioglitazone compared with metformin , General • None reported Cardiac toxicity • No fluid retention or HF Drug discontinuation • Patient decision ( n = 1 ) • Loss of glycemic control ( n = 2 ) • Hypertriglyceridemia requiring therapy ( n = 1 ) • Incidentaloma ( n = 1 ).

Techniques: Control, Clinical Proteomics, Concentration Assay