Chronic administration of Sildenafil improves markers of endothelial function in men with Type 2 diabetes

Diabet Med. 2008 Jan;25(1):37-44. doi: 10.1111/j.1464-5491.2007.02298.x.

Abstract

Objective: Diabetic patients have a reduced endothelial response to phosphodiesterase-5 inhibitors. The aim of this study was to determine the effects of chronic therapy with sildenafil on endothelial function in patients with Type 2 diabetes mellitus (DM2).

Methods: In a double-blind, placebo-controlled parallel design, 20 patients without erectile dysfunction randomly received a loading dose of sildenafil (100 mg) for 3 days, followed by either sildenafil 25 mg three times a day (t.d.s.) for 4 weeks or sildenafil 25 mg t.d.s. for 4 days followed by placebo t.d.s. for 3 weeks.

Results: After 1 week, flow-mediated dilatation (FMD) improved significantly (> 50% compared with baseline) in patients allocated to both sildenafil arms (62 and 64%, respectively). In patients allocated to chronic sildenafil, a progressive increase in percentage of patients with FMD improvement was noted (78, 86 and 94% at 2, 3 and 4 weeks, respectively) while a progressive decrease in the placebo group occurred (45, 18 and 6% at 2, 3 and 4 weeks, respectively). At the end of the study, a significant improvement in FMD compared with baseline was noted after chronic sildenafil (FMD from 6.8 +/- 0.5 to 12.5 +/- 0.7%, P = 0.01 vs. baseline). A decrease in endothelin-1 levels and an increase in nitrite/nitrate levels were found after chronic sildenafil; significant changes from baseline in C-reactive protein, interleukin 6, intercellular adhesion molecule and vascular adhesion molecule levels were also found.

Conclusions: In DM2 patients, daily sildenafil administration improves endothelial function and reduces markers of vascular inflammation, suggesting that the diabetes-induced impairment of endothelial function may be improved by prolonged phosphodiesterase-5 inhibition.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / metabolism
  • Brachial Artery / physiopathology
  • C-Reactive Protein / metabolism
  • Cell Adhesion Molecules / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetic Angiopathies / blood
  • Diabetic Angiopathies / drug therapy*
  • Diabetic Angiopathies / physiopathology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Endothelium, Vascular / drug effects*
  • Humans
  • Interleukin-6 / metabolism
  • Male
  • Middle Aged
  • Phosphodiesterase Inhibitors / administration & dosage*
  • Piperazines / administration & dosage*
  • Purines / administration & dosage
  • Sildenafil Citrate
  • Sulfones / administration & dosage*
  • Treatment Outcome
  • Vasodilation / drug effects
  • Vasodilator Agents / administration & dosage*

Substances

  • Biomarkers
  • Cell Adhesion Molecules
  • Interleukin-6
  • Phosphodiesterase Inhibitors
  • Piperazines
  • Purines
  • Sulfones
  • Vasodilator Agents
  • C-Reactive Protein
  • Sildenafil Citrate