Trial reportThe Journal of clinical endocrinology and metabolism2015
Treatment with Sildenafil Improves Insulin Sensitivity in Prediabetes: A Randomized, Controlled Trial.
Trial report in The Journal of clinical endocrinology and metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01409993 (Renin-Angiotensin and Fibrinolysis in Humans), which is not on this map. Cited by 37 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Renin-Angiotensin and Fibrinolysis in Humans: Effect of Long-Term PDE5 Inhibition on Glucose Homeostasis
Who cites it
37 citing papers in PubMed, 75 citations in OpenAlex.
- Tadalafil improves lean mass and endothelial function in nonobese men with mild ED/LUTS: in vivo and in vitro characterization.Endocrine · 2017Trial
- A Common CD36 Variant Influences Endothelial Function and Response to Treatment with Phosphodiesterase 5 Inhibition.The Journal of clinical endocrinology and metabolism · 2016Trial
- Increased cGMP improves microvascular exercise training adaptations in diet-induced obesity.American journal of physiology. Endocrinology and metabolism · 2025Article
- Sildenafil amplifies calcium influx and insulin secretion in pancreatic β cells.Physiological reports · 2024Article
- Cone photoreceptor phosphodiesterase PDE6H inhibition regulates cancer cell growth and metabolism, replicating the dark retina response.Cancer & metabolism · 2024Article
- PDE5 inhibitor potentially improves polyuria and bladder storage and voiding dysfunctions in type 2 diabetic rats.PloS one · 2024Article
- Endothelial Dysfunction in Obesity and Therapeutic Targets.Advances in experimental medicine and biology · 2024Review
- Chronic sildenafil citrate use decreases retinal vascular endothelial growth factor expression in diabetic rats: a pilot study.International journal of retina and vitreous · 2023Article
- Article
- The efficacy of PDE5 inhibitors in diabetic patients.Andrology · 2023Review
- The Impact of Sildenafil on Ischemic Outcomes in Patients with Pulmonary Hypertension - A Nationwide Cohort Study.Acta Cardiologica Sinica · 2022Article
- Emerging therapies: The potential roles SGLT2 inhibitors, GLP1 agonists, and ARNI therapy for ARNI pulmonary hypertension.Pulmonary circulation · 2022Review
- The Aggressive Diabetic Kidney Disease in Youth-Onset Type 2 Diabetes: Pathogenetic Mechanisms and Potential Therapies.Medicina (Kaunas, Lithuania) · 2021Review
- Sildenafil augments fetal weight and placental adiponectin in gestational testosterone-induced glucose intolerant rats.Toxicology reports · 2021Article
- Established and emerging therapeutic uses of PDE type 5 inhibitors in cardiovascular disease.British journal of pharmacology · 2020Review
- Role of Phosphodiesterase in the Biology and Pathology of Diabetes.International journal of molecular sciences · 2020Review
- Regulating cellular cyclic adenosine monophosphate: "Sources," "sinks," and now, "tunable valves".Wiley interdisciplinary reviews. Systems biology and medicine · 2020Review
- Should All Men with Type 2 Diabetes Be Routinely Prescribed a Phosphodiesterase Type 5 Inhibitor?The world journal of men's health · 2020Review
- Primary Aldosteronism Decreases Insulin Secretion and Increases Insulin Clearance in Humans.Hypertension (Dallas, Tex. : 1979) · 2020Article
- Sildenafil for the Treatment of Alzheimer's Disease: A Systematic Review.Journal of Alzheimer's disease reports · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
contextSildenafil increases insulin sensitivity in mice. In humans, phosphodiesterase 5 inhibition improves disposition index, but the mechanism of this effect has not been elucidated and may depend on duration. In addition, increasing cyclic GMP without increasing nitric oxide could have beneficial effects on fibrinolytic balance.
objectiveThe objective was to test the hypothesis that chronic phosphodiesterase 5 inhibition with sildenafil improves insulin sensitivity and secretion without diminishing fibrinolytic function.
designThis was a randomized, double-blind, placebo-controlled study.
settingThis trial was conducted at Vanderbilt Clinical Research Center.
participantsParticipants included overweight individuals with prediabetes.
interventionsSubjects were randomized to treatment with sildenafil 25 mg three times a day or matching placebo for 3 months. Subjects underwent a hyperglycemic clamp prior to and at the end of treatment.
main outcome measuresThe primary outcomes of the study were insulin sensitivity and glucose-stimulated insulin secretion.
resultTwenty-one subjects completed each treatment arm. After 3 months, the insulin sensitivity index was significantly greater in the sildenafil group compared to the placebo group by 1.84 mg/kg/min per μU/mL*100 (95% confidence interval, 0.01 to 3.67 mg/kg/min per μU/mL*100; P = .049), after adjusting for baseline insulin sensitivity index and body mass index. In contrast, there was no effect of 3-month treatment with sildenafil on acute- or late-phase glucose-stimulated insulin secretion (P > .30). Sildenafil decreased plasminogen activator inhibitor-1 (P = .01), without altering tissue-plasminogen activator. In contrast to placebo, sildenafil also decreased the urine albumin-to-creatinine ratio from 12.67 ± 14.67 to 6.84 ± 4.86 μg/mg Cr. This effect persisted 3 months after sildenafil discontinuation.
conclusionsThree-month phosphodiesterase 5 inhibition enhances insulin sensitivity and improves markers of endothelial function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.