Pioglitazone, Lipotoxicity, and Heart Failure With Preserved Ejection Fraction (HFpEF)
Our goal of the study is to learn the effects of the diabetes medication named Pioglitazone, in type-2 diabetic obese participants with Heart failure. The main question it aims to answer are: 1. To demonstrate that impaired mitochondrial function leading to reduced ATP generation plays a key pathophysiologic role in the development of heart failure with preserved ejection fraction (HFpEF) in obese type 2 diabetic (T2D) individuals. 2. To demonstrate that pioglitazone, improves diastolic (as well as systolic) function by improving myocardial insulin sensitivity and by reducing both myocardial and epicardial fat content.
• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged 30-70 years
• Body Mass Index (BMI) of 27.5-40kg/m²
• HbA1c of 6.5 to 10%
• Blood pressure of less than or equal to 145/65mmHg
• eGFR greater than 45 ml/min/1.73m²
• Subject must have HFpEF (EF \> 50% by ECHO screening)
• NYHA class II-III heart failure
⁃ Only T2D patients treated with diet/exercise, metformin, sulfonylurea, metformin/SU, DPP4i or insulin will be studied.
⁃ For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional \[4 weeks\] after the end of study participation.
⁃ For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner.