Effect of phosphodiesterase-5 inhibitors on glycemic control in person with type 2 diabetes mellitus: A systematic review and meta-analysis

Chronic use of phosphodiesterase-5 inhibitors (PDE-5i) has been shown to improve insulin action on muscle glucose uptake by the prolongation of nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase (PKG) signalling. AIMS: As the effects of PDE-5i on glycemic control in person with type 2 diabetes mellitus (T2DM) have not been systematically explored, we conducted a meta-analysis of available randomized controlled trials (RCTs). METHODS: A literature search was performed through electronic databases including MEDLINE (Pubmed), The Cochrane Library, SCOPUS, Web of Science, CINAHL, www.clinicaltrials.gov and www.clinicaltrialresults.org until April 2016 without language restriction. Studies were included if they met the following criteria: (i) RCTs of the chronic use of PDE-5i compared with placebo or no active treatment in T2DM patients (ii) reporting of HbA1c or glycated haemoglobin or fasting plasma glucose (FPG). RESULTS: Four studies involving a total of 198 patients fit into the inclusion criteria. All included studies used the same PDE-5i, sildenafil. Reports of HbA1c were analysed as only one study reported FPG. PDE-5i had no beneficial effect on HbA1c with weighted mean difference (WMD) of 0.17% (95% CI, −0.64 to 0.97). CONCLUSION: This meta-analysis suggests that large and well-controlled studies are warranted to shed light on the effect of PDE-5i on glycemic control in people with type 2 diabetes mellitus.