Effect of Phosphodiesterase Inhibition on Insulin Resistance in Obese Individuals
Open accessAbstract
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.
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Ho and colleagues reported that tadalafil tended to improve insulinogenic index in insulin-resistant subjects undergoing OGTT.
“Ho and colleagues reported that twelve-week treatment with tadalafil improved DI and oral DI, and tended to improve insulinogenic index in insulin-resistant subjects undergoing OGTT; tadalafil also improved insulin sensitivity among severely obese participants.233”
From The Vasculature in Prediabetes (2018) · cites this paper as [233]
Ho and colleagues reported that twelve-week treatment with tadalafil improved DI and oral DI in insulin-resistant subjects undergoing OGTT.
“Ho and colleagues reported that twelve-week treatment with tadalafil improved DI and oral DI, and tended to improve insulinogenic index in insulin-resistant subjects undergoing OGTT; tadalafil also improved insulin sensitivity among severely obese participants.233”
From The Vasculature in Prediabetes (2018) · cites this paper as [233]
Ho and colleagues reported that tadalafil improved insulin sensitivity among severely obese participants.
“Ho and colleagues reported that twelve-week treatment with tadalafil improved DI and oral DI, and tended to improve insulinogenic index in insulin-resistant subjects undergoing OGTT; tadalafil also improved insulin sensitivity among severely obese participants.233”
From The Vasculature in Prediabetes (2018) · cites this paper as [233]
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- Authors
- 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.
- Affiliations
- Boston University (US)
- University of Alabama at Birmingham (US)
- Massachusetts General Hospital (US)
- Mount Auburn Hospital (US)
- Brigham and Women's Hospital (US)
- Diabetes Center, Massachusetts General Hospital, Boston, MA
- Broad Institute (US)
- Vanderbilt University (US)
- ORCID
- Venue
- Journal of the American Heart Association
- Published
- 2014-09-16
- Volume
- 3
- Issue
- 5
- Pages
- e001001-e001001
- ISSN
- 2047-9980 (ISSN-L)
- PMC
- PMC4323801
- OpenAlex
- W2157833783
- Cited by
- 39
- References
- 29
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 5 · 2019: 5 · 2018: 4 · 2017: 4 · 2016: 5 · 2015: 3 · 2014: 1 · 2013: 1
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Journal of the American Heart Association (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- Brigham and Women's Hospital
- National Heart, Lung, and Blood Institute (R01HL086875, K23HL116780, R01HL098283, R01HL113933)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phosphodiesterase function and regulation
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- phosphodiesterase-5 inhibition, tadalafil, insulin resistance, obesity, morbid obesity, cGMP signaling, beta-cell compensation, disposition index, glucose tolerance
- MeSH terms
- Tadalafil, Adolescent, Adult, Blood Glucose, Boston, Carbolines, Double-Blind Method, Female, Humans, Insulin, Insulin Resistance, Male, Middle Aged, Obesity, Pilot Projects, Severity of Illness Index, Time Factors, Biomarkers, Body Mass Index, Treatment Outcome, Insulin-Secreting Cells, Young Adult, Phosphodiesterase 5 Inhibitors
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