PDE-5 Inhibitors Get Thumbs Up for Diabetes-Related Erectile Dysfunction

HAIFA, Israel, Jan. 24 -- The phosphodiesterase-5 (PDE-5) inhibitors are both safe and effective for treating erectile dysfunction in men with both type 1 and type 2 diabetes, according to a meta-analysis.

The meta-analysis of randomized controlled trials of Viagra (sildenafil), Levitra (vardenafil), and Cialis (tadalafil), as a group, found that men who took the drugs had 26.7% more successful intercourse attempts than controls, reported Moshe Vardi, M.D., and Assaf Nini from the Lady Davis Carmel Medical Center.

"It is clear from the meta-analysis presented that PDE-5 inhibitors should be considered a primary treatment for erectile dysfunction in diabetic men," the authors wrote in the first 2007 issue of the Cochrane Database of Systematic Reviews.

"They have proved to be effective and safe. It seems that their effect may wane in low doses in patients with uncontrolled diabetes, with higher baseline glycated hemoglobin. Higher doses may be required for this particular subgroup."

The results aren't particularly surprising, "but give strength to the general notion that this class of drugs is efficient and safe for this specific wide population," acknowledged Dr. Vardi.

"I prescribe PDE-5 inhibitors every day to people with diabetes," said John Buse, M.D., director of the Diabetes Care Center at the University of North Carolina, in a statement "But whether they are safe is the essential quandary of all medical care. We make our best guesses based on imperfect information, hopes and fears. And then we monitor progress."

To see whether the widely prescribed drugs were both safe and effective in men with diabetes, the reviewers conducted a meta-analysis of eight randomized trials comparing the three PDE-5 inhibitors with placebo.

In all, the trials involved 1,717 men, 80% of them with type 2 diabetes and the remainder with type 1. A total of 976 men were randomly assigned to receive a PDE-5 inhibitor, and 741 were designated as controls.

Most of the studies ran 12 weeks, and there were no significant differences between active drug and control groups in age, medical history, medication use, or severity or duration of diabetes or erectile dysfunction.

The studies used the 1993 NIH consensus definition of erectile dysfunction as "the inability to achieve and maintain an erection sufficient to permit satisfactory sexual intercourse."

The primary outcome measure was ability to achieve penile rigidity satisfactory for penetration and sufficiently prolonged to enable sexual intercourse to be completed. The success of the outcome was assessed through validated questionnaires and scales for erectile function, sexual function, quality of life, and global efficacy.

Other outcomes included adverse events, morbidity, and all-cause mortality, and data were adjusted for patient compliance, glycated hemoglobin (HbA1c) levels or other measures of glycemic control throughout the trials, and changes in concomitant medications.

The reviewers found that in the five of the eight studies, participants were asked questions three and four on the International Index of Erectile Function, regarding frequency of penetration during (question three) and maintaining erection to completion of intercourse (question four). The weighted mean difference at the end of the study for question three was 0.9 (95% confidence interval, 0.8 to 1.1), and for question four was 1.1 (95% CI, 1.0 to 1.2) at the end of the study period, both in favor of the drug group.

At the end of the study, the weighted mean difference for the erectile dysfunction domain on the index was 6.6 (95% CI, 5.2 to 7.9) in favor of the PDE-5 inhibitors arm.

Men were who took PDE-5 inhibitors were about four times more likely than men on placebo to answer yes to the question "did the treatment improve your erections?" (relative risk 3.8, 95% CI, 3.1 to 4.5)

When it came to successful intercourse attempts, the weighted mean difference was 26.7, (95% CI, 23.1 to 30.3) in favor of the PDE-5 inhibitor.

There were no deaths reported in any of the included trials.

The overall risk ratio for any adverse reaction among PDE-5 users versus controls was 4.8 (95% CI, 3.74 to 6.16). Adverse effects included cardiovascular events, which occurred in 10 patients (7%) in one study of Viagra. The events included four incidents of chest pain, of which two were myocardial infarctions with a documented ST-elevation, two cases of congestive heart failure, and four cases of hypertension.

The most frequently reported adverse event among PDE-5 users was headache, with a risk ratio of 3.66 (95%CI, 2.51 to 5.35), followed by flushing (relative risk 13.21, 95% CI, 6.01 to 29.03).

Other events, included upper respiratory tract complaints and flu-like syndromes, dyspepsia, myalgia, abnormal vision and back pain.

"Unfortunately, we found no head-to-head comparisons between the three available PDE-5 inhibitors, and no trials comparing them with other available therapeutic options," the authors wrote. "Another issue of interest which is yet in its infancy is the effect of PDE-5 inhibitors on female sexual dysfunction, particularly diabetic women."

They noted that one limitation of the review was that none of the studies included showed a low risk for bias, which may reflect study design flaws, "or merely lack of adequate reporting. Nevertheless, sensitivity analyses taking account of specific quality criteria and excluding trials with inadequate reporting did not influence the robustness of the results."