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Effect of phosphodiesterase inhibition on insulin resistance in obese individuals

Jennifer E Ho1, Pankaj Arora2, Geoffrey A Walford3

  • 1Cardiovascular Medicine Section, Department of Medicine, Boston University School of Medicine, Boston, MA (J.E.H.).

Journal of the American Heart Association
|September 13, 2014
PubMed
Abstract

Insights

Tadalafil did not improve insulin resistance in obese individuals. However, it showed potential benefits for beta-cell compensation, especially in those with severe obesity, warranting further research into cGMP modulation.

Area of Science:

  • Cardiovascular Science
  • Metabolic Health
  • Pharmacology

Background:

  • Obesity is a significant risk factor for cardiometabolic diseases, including insulin resistance (IR) and type 2 diabetes.
  • Cyclic guanosine monophosphate (cGMP) signaling pathways are implicated in regulating energy balance, IR, and glucose metabolism.
  • Phosphodiesterase-5 (PDE5) inhibitors, such as tadalafil, modulate cGMP levels.

Purpose of the Study:

  • To investigate the effects of tadalafil, a PDE5 inhibitor, on insulin resistance in a pilot study involving obese, non-diabetic individuals.
  • To assess the impact of tadalafil on glucose metabolism and beta-cell function in the context of obesity.

Main Methods:

  • A randomized, double-blind, placebo-controlled trial was conducted with 53 obese adults (age 18-50) with elevated fasting insulin.
  • Participants received either tadalafil (20 mg daily) or a placebo for 3 months.
  • Oral glucose tolerance tests were performed to evaluate insulin resistance (using homeostatic model assessment for IR) and beta-cell compensation (using oral disposition index).

Main Results:

  • Overall, tadalafil did not significantly improve measures of insulin resistance compared to placebo.
  • In participants with severe obesity (BMI ≥36.2 kg/m²), tadalafil treatment was associated with improved insulin resistance (P=0.02).
  • Tadalafil significantly improved beta-cell compensation (oral disposition index) in both the overall sample (P=0.009) and the severe obesity subgroup (P=0.01).

Conclusions:

  • This pilot study suggests tadalafil does not improve insulin resistance in obese individuals but may offer benefits for beta-cell compensation.
  • The findings indicate a potential role for cGMP modulation in managing metabolic dysfunction, particularly in severe obesity.
  • Further research is warranted to explore the therapeutic potential of tadalafil and other cGMP modulators in obesity-related metabolic disorders.
Keywords:
cGMPinsulin resistanceobesityphosphodiesterase type 5 inhibition

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