Effect of phosphodiesterase inhibition on insulin resistance in obese individuals

Jennifer E. Ho, Pankaj Arora, Geoffrey A. Walford, Anahita Ghorbani, Derek P. Guanaga, Bishnu P. Dhakal, Daniel I. Nathan, Emmanuel S. Buys, Jose C. Florez, Christopher Newton-Cheh, Gregory D. Lewis, Thomas J. Wang

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Background-Obesity is associated with cardiometabolic disease, including insulin resistance (IR) and diabetes. Cyclic guanosine monophosphate (cGMP) signaling affects energy balance, IR, and glucose metabolism in experimental models. We sought to examine effects of phosphodiesterase-5 inhibition with tadalafil on IR in a pilot study of obese nondiabetic individuals. Methods and Results-We conducted a randomized, double-blinded, placebo-controlled trial of adults age 18 to 50 years with obesity and elevated fasting insulin levels (≥10 μU/mL). Participants were randomized to tadalafil 20 mg daily or placebo for 3 months. Oral glucose tolerance tests were performed, and the effect of tadalafil on IR was examined. A total of 53 participants (mean age, 33 years; body mass index [BMI], 38 kg/m2) were analyzed, 25 randomized to tadalafil and 28 to placebo. In the overall sample, measures of IR did not differ between tadalafil and placebo groups at 3 months. However, in individuals with severe obesity (BMI ≥36.2 kg/m2), tadalafil use was associated with improved IR (homeostatic model assessment for IR), compared to placebo (P=0.02, respectively). Furthermore, one measure of ß-cell compensation for IR (oral disposition index) improved with tadalafil in the overall sample (P=0.009) and in the subgroup with severe obesity (P=0.01). Conclusion-Results of this pilot study did not show improvements in IR with tadalafil, compared to placebo. However, tadalafil may have favorable effects on ß-cell compensation, particularly in individuals with severe obesity. Future studies evaluating the potential metabolic benefits of cGMP modulation in obesity are warranted.

Original languageEnglish (US)
Article numbere001001
JournalJournal of the American Heart Association
Volume3
Issue number5
DOIs
StatePublished - 2014

Keywords

  • Insulin resistance
  • Obesity
  • Phosphodiesterase type 5 inhibition
  • cGMP

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Ho, J. E., Arora, P., Walford, G. A., Ghorbani, A., Guanaga, D. P., Dhakal, B. P., Nathan, D. I., Buys, E. S., Florez, J. C., Newton-Cheh, C., Lewis, G. D., & Wang, T. J. (2014). Effect of phosphodiesterase inhibition on insulin resistance in obese individuals. Journal of the American Heart Association, 3(5), [e001001]. https://doi.org/10.1161/JAHA.114.001001