Metformin for Pulmonary Hypertension HFpEF

Prior treatment

• Currently taking metformin or history of intolerance to metformin or contraindication to taking metformin;

Other illness

• 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;
• Known type 1 diabetes

Lab values

• Hemoglobin A1C \> 10;
• Ejection Fraction \< 50%
• 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

Age

• Age less than 18 years;

Other

• Systemic sitting blood pressure \< 110 mmHg systolic or \< 60 mm Hg diastolic at Screening;
• Positive urine pregnancy test or breastfeeding

• 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