Overview

The main objective of this study is to determine the clinical efficacy of metformin versus placebo and the therapeutic response with regards to functional capacity and hemodynamics in PH-HFpEF.

Eligibility

Inclusion Criteria:

2. PH-HFpEF Confirmed diagnosis by RHC within the past 6 months:

        Mean Pulmonary Arterial Pressure (mPAP) ≥ 25 mm Hg AND Pulmonary artery wedge pressure
        (PAWP) ≥ 15 mm Hg AND Transpulmonary Gradient (TPG) ≥ 12 mm Hg
        OR Exercise measurements
        Mean Pulmonary Arterial Pressure (mPAP) ≥ 30 mm Hg AND Pulmonary artery wedge pressure
        (PAWP) ≥ 20 mm Hg AND PA calculation (change in mPAP/change in cardiac output) = ≥3
        mmHg/L/min
        3. Three or more features of metabolic syndrome defined as:
        Body Mass Index (BMI) ≥ 30 kg/m² Systolic blood pressure (BP) ≥ 130 mm Hg and/or diastolic
        BP ≥ 85 mm Hg Elevated waist circumference > 102 cm in men and > 88 cm in women Fasting
        triglyceride (TG) level over 150 mg/dl High-density lipoprotein <40 mg/dL in men or < 50
        mg/dL in women
        Exclusion Criteria:
          1. Age less than 18 years;
          2. Uncontrolled systemic hypertension based on repeated measurement of sitting systolic
             blood pressure >170 mm Hg or sitting diastolic blood pressure >95 mm Hg at Screening;
          3. Systemic sitting blood pressure < 110 mmHg systolic or < 60 mm Hg diastolic at
             Screening;
          4. Hemoglobin A1C > 10;
          5. Currently taking metformin or history of intolerance to metformin or contraindication
             to taking metformin;
          6. Known type 1 diabetes
          7. Positive urine pregnancy test or breastfeeding
          8. Ejection Fraction < 50%
          9. Dementia;
        11. End-stage malignancy; 12. Major cardiovascular event or procedure within 6 weeks prior
        to enrollment; 13. Severe valvular disease; 14. Other severe acute or chronic medical,
        psychiatric or laboratory abnormality that may increase the risk associated with study
        participation or investigational product administration or may interfere with the
        interpretation of study results and, in the judgment of the investigator, would make the
        subject inappropriate for entry into this study or would prevent completion of the study;
        15. Current Smoker; 16. Hemoglobin <9 g/dL; 17. Estimated glomerular filtration rate (eGFR)
        <30 mL/min/1.73 m2; 18. Receipt of an investigational product or device, or participation
        in a drug research study within a period of 15 days 19. <3 months of stable dose of PDE5i