Abstract 063: Phosphodiesterase 5 Inhibition Improves Insulin Sensitivity and Disposition Index in Prediabetes without Altering Glucose-Stimulated Insulin Secretion
Chronic administration of the PDE5 inhibitor sildenafil citrate improves insulin sensitivity in high fat-fed mice. A small study in patients with metabolic syndrome found that one-month treatment with tadalafil with or without ACE inhibition improves disposition index (DI) and β-cell function, as measured by IVGTT. We report the results of a randomized, double-blind, placebo-controlled study of the effect of 3-month treatment with sildenafil (25mg t.i.d.) on insulin sensitivity and secretion assessed using hyperglycemic clamps in individuals with impaired fasting glucose and/or impaired glucose tolerance. Among 51 subjects randomized, 21 subjects completed sildenafil treatment [8 men, 2 black Americans, body mass index (BMI) 35.7±6.8 Kg/m2], and 21 completed placebo treatment (8 men, 6 black Americans, BMI 36.4±6.6 Kg/m2). There was no significant difference in acute- or late-phase glucose-stimulated insulin secretion (GSIS) between groups. In contrast, insulin sensitivity index (ISI) and DI were significantly higher in the sildenafil group (Figure, adjusted means and 95% CI after controlling for baseline measurements and BMI, *P<0.05). Sildenafil did not significantly affect blood pressure or heart rate compared to placebo. These data suggest that pharmacological strategies to increase cGMP enhance insulin sensitivity. Additional studies are needed to determine whether PDE5 inhibition prevents incident diabetes in high risk populations.
Author Disclosures: C.E. Ramirez: None. C. Shibao: None. H. Nian: None. C. Yu: None. J.M. Luther: None. N.J. Brown: None.
- © 2014 by American Heart Association, Inc.