Diabetes mellitus (DM) is associated to endothelial dysfunction, reducing nitric oxide (NO)-dependent vasodilation and increasing production of pro-inflammatory factors, leading to increased long-term cardiovascular risk. Since the effects of phosphodiesterase-5 inhibitors (PDE5i) on endothelial function have not been systematically investigated, we conducted a meta-analysis of available randomised clinical trials (RCTs). A thorough search of the literature was carried out. Relevant studies were considered according to RCT study design, enrolment of men with Type 2 DM, chronic administration of PDE5i and evaluation of endothelial function through both hemodynamic and endothelial inflammation-related parameters. 15 studies fulfilled the eligibility criteria but only 6 RCTs met the inclusion criteria and were analysed for 476 diabetic men, 239 randomized to Sildenafil and 237 to placebo, respectively. Four RCTs evaluated flow-mediated dilation (FMD), demonstrating a weighted mean increase of 2.19% (CI95%: 0.48-3.90). This result showed a high heterogeneity (I2:98%). Thus, a further sub-group meta-analysis was performed, excluding one study through funnel plot. This analysis confirmed a significant, Sildenafil-related FMD improvement. Sildenafil improved endothelin(ET)-1 and high sensitivity C-reactive protein of about -0.94pg/mL and -0.36mg/L, respectively, not reaching statistical significance (p=0.69 and p=0.22, respectively). Finally, Sildenafil administration significantly reduced interleukin-6 (IL-6) serum levels (-0.82 pg/mL; CI95%:-1.58 to -0.07). This meta-analysis suggests a beneficial effect of chronic PDE5i administration on endothelial function. Chronic Sildenafil administration seems to improve hemodynamic (FMD), and serum pro-inflammatory makers (IL-6) in diabetic men. Larger studies are needed to confirm the effects of chronic PDE5i on endothelial function.
THERAPY OF ENDOCRINE DISEASE: Effects of chronic use of phosphodiesterase inhibitors on endothelial markers in type 2 diabetes mellitus: a meta-analysis / D., Santi; Giannetta, Elisa; Isidori, Andrea; C., Vitale; Aversa, Antonio; M., Simoni. - In: EUROPEAN JOURNAL OF ENDOCRINOLOGY. - ISSN 1479-683X. - 172:3(2014), pp. R103-R114. [10.1530/eje-14-0700]
THERAPY OF ENDOCRINE DISEASE: Effects of chronic use of phosphodiesterase inhibitors on endothelial markers in type 2 diabetes mellitus: a meta-analysis.
GIANNETTA, ELISA;ISIDORI, Andrea;AVERSA, Antonio;
2014
Abstract
Diabetes mellitus (DM) is associated to endothelial dysfunction, reducing nitric oxide (NO)-dependent vasodilation and increasing production of pro-inflammatory factors, leading to increased long-term cardiovascular risk. Since the effects of phosphodiesterase-5 inhibitors (PDE5i) on endothelial function have not been systematically investigated, we conducted a meta-analysis of available randomised clinical trials (RCTs). A thorough search of the literature was carried out. Relevant studies were considered according to RCT study design, enrolment of men with Type 2 DM, chronic administration of PDE5i and evaluation of endothelial function through both hemodynamic and endothelial inflammation-related parameters. 15 studies fulfilled the eligibility criteria but only 6 RCTs met the inclusion criteria and were analysed for 476 diabetic men, 239 randomized to Sildenafil and 237 to placebo, respectively. Four RCTs evaluated flow-mediated dilation (FMD), demonstrating a weighted mean increase of 2.19% (CI95%: 0.48-3.90). This result showed a high heterogeneity (I2:98%). Thus, a further sub-group meta-analysis was performed, excluding one study through funnel plot. This analysis confirmed a significant, Sildenafil-related FMD improvement. Sildenafil improved endothelin(ET)-1 and high sensitivity C-reactive protein of about -0.94pg/mL and -0.36mg/L, respectively, not reaching statistical significance (p=0.69 and p=0.22, respectively). Finally, Sildenafil administration significantly reduced interleukin-6 (IL-6) serum levels (-0.82 pg/mL; CI95%:-1.58 to -0.07). This meta-analysis suggests a beneficial effect of chronic PDE5i administration on endothelial function. Chronic Sildenafil administration seems to improve hemodynamic (FMD), and serum pro-inflammatory makers (IL-6) in diabetic men. Larger studies are needed to confirm the effects of chronic PDE5i on endothelial function.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.