Endothelin antagonism reduces hemoglobin A1c in patients with pulmonary hypertension.

Our lab recently reported that blockade of endothelin-1 (ET-1) receptors attenuates insulin resistance in obese mice; therefore, we hypothesized that patients taking ET-1 receptor antagonists (ERA) will have improved glycemic control. University of Mississippi Medical Center (2013-2020) EPIC data were extracted from patients ≥18 years old with a clinical diagnosis of pulmonary hypertension (FDA indication for ERA use) and at least two clinical visits within 2 years. Patients prescribed ERAs (n=11) were similar in age (6114 vs. 6014 yr), BMI (348 vs. 3511 kg/m2), diabetes prevalence (73% vs. 80%, p=0.59), and follow-up time (20974 vs. 283180 days) compared to patients not taking ERAs (n=137). There was a small but similar decrease in BMI at follow-up in the ERA (-1.93 kg/m2) and control patients (-1.65 kg/m2). At follow-up, HbA1c significantly decreased -1211% of baseline in patients taking ERA while this did not occur in the control patients (220% increase in HbA1c). In the whole population, baseline HbA1c and ERA prescription predicted the fall in HbA1c, while there was no significant association with demographics, diabetes prevalence, and diabetic treatment. These data suggest a potential role of ET-1 in promoting insulin resistance and warrants further investigation into using these drugs for glycemic control.