Effect of phosphodiesterase inhibition on insulin resistance in obese individuals.

J Am Heart Assoc
Authors
Keywords
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/m(2)) 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/m(2)), tadalafil use was associated with improved IR (homeostatic model assessment for IR), compared to placebo (P=0.02, respectively). Furthermore, one measure of β-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 β-cell compensation, particularly in individuals with severe obesity. Future studies evaluating the potential metabolic benefits of cGMP modulation in obesity are warranted.

CLINICAL TRIAL REGISTRATION URL: ClinicalTrials.gov. Unique Identifier: NCT01444651.

Year of Publication
2014
Journal
J Am Heart Assoc
Volume
3
Issue
5
Pages
e001001
Date Published
2014 Sep 11
ISSN
2047-9980
URL
DOI
10.1161/JAHA.114.001001
PubMed ID
25213566
PubMed Central ID
PMC4323801
Links
Grant list
R01-HL113933 / HL / NHLBI NIH HHS / United States
K23-HL116780 / HL / NHLBI NIH HHS / United States
R01-HL086875 / HL / NHLBI NIH HHS / United States
K23 HL116780 / HL / NHLBI NIH HHS / United States
R01-HL098283 / HL / NHLBI NIH HHS / United States