Oral sildenafil in the treatment of erectile dysfunction in diabetic men
A randomized double-blind and placebo-controlled study
Mohammad R. Safarinejad*
Department of Urology, Military University of Medical Sciences, P.O. Box 19395-1849, Tehran, Iran
Received 14 February 2003; received in revised form 6 April 2003; accepted 15 April 2003
Purpose: To determine the efficacy and safety of oral sildenafil citrate in the treatment of erectile dysfunction (ED) in diabetic men.
Materials and methods: In a randomized, double-blind, placebo-controlled, and fixed-dose study, a total of 282 men (mean age, 46.4 years)
with ED (mean duration, 3.6 years) and diabetes (mean duration, 11 years) were randomly assigned to receive 100 mg sildenafil (n=144) or
placebo (n=138) approximately 1 h before planned sexual activity, but not more than once daily, for 16 weeks. The efficacy of two
treatments was assessed using responses to the International Index of Erectile Function (IIEF) questionnaire. Results: Two hundred sixty-two
(93%) of men completed the study (134/144 in the sildenafil group, 128/138 in the placebo group). Positive clinical results were obtained in
68 (51%) of 134 patients in the sildenafil group compared with 14 (11%) of 128 patients in the placebo group (P<.003). Fifty-nine percent
of the patients reported at least one successful attempt at sexual intercourse in the sildenafil group as compared with 21% successful attempts
for the placebo group (P<.002). Drug-related adverse effects occurred in 32 (22%) of 144 patients taking sildenafil and 4 (3%) of 138
patients receiving placebo. The most common adverse events were headache (20% sildenafil, 2% placebo), flushing (19% sildenafil, 0%
placebo), dyspnea (9% sildenafil, 2% placebo), rhinitis (6% sildenafil, 0% placebo), and cardiovascular effects (7% sildenafil, 0% placebo).
Of patients taking sildenafil, four (2.7%) developed new chest pains, with documented myocardial infarction in two. Conclusion: Oral
sildenafil is a moderately effective treatment for ED in men with diabetes. The response rate was lower and cardiovascular events were higher
than previously reported in nondiabetic patients.
D 2004 Elsevier Inc. All rights reserved.
Keywords: Sildenafil; Penile erection; Erectile dysfunction; Diabetes
Erectile dysfunction (ED) is a common complication of
diabetes and an important cause of decreased quality of life
in men with diabetes (NIH Consensus Conference, 1993).
The prevalence of ED of any degree in men aged 40 to 70
years was estimated to be 52% in the Massachusetts Male
Aging Study, with a prevalence of 25% for moderate ED
and 10% for complete ED (Feldman, Goldstein, Hatzichris-
tou, Krane, & McKinlay, 1994). ED occurs at an earlier age
in men with diabetes than in men in the general population
(Whitehead & Klyde, 1990), and its frequency has been
reported to be higher in people with diabetes compared with
those without diabetes in some but not all studies (Fairburn,
McCulloch, & Wu, 1982; Malgrange, Coulon, & Leuteneg-
ger, 1990; Miccoli et al., 1987). ED in diabetic men has
been associated with diabetic neuropathy (Saenz de Tejada
& Goldstein, 1988), peripheral vascular disease (Braunstein,
1987), poor glycemic control (McCulloch, Young, Prescott,
Campbell, & Clarke, 1984), use of specific types of med-
ications (Muller, El-Damanhoury, Ruth, & Lue, 1991;
Wiles, 1992), and increased age (McCulloch et al., 1984).
In response to sexual stimulation, nonadrenergic non-
cholinergic nerves and endothelial cells of the arterioles in
the penis release nitric oxide. This in turn stimulates the
formation of cyclic 3V,5V-guanosine monophosphate (cGMP)
by guanylate cyclase. cGMP then affects the relaxation of
the smooth muscles of the corpora cavernosa. cGMP is
hydrolyzed by cGMP-specific phosphodiesterase type 5
(PDE 5), the predominant PDE isoenzyme of the corpus
cavernosum (Boolell, Allen, Ballard, et al., 1996). Sildenafil
is a potent and competitive inhibitor of the PDE 5.
Sildenafil has been shown to be an effective and well-
tolerated treatment in patients with ED of various etiologies
1056-8727/04/$ – see front matter D 2004 Elsevier Inc. All rights reserved.
* Tel.: +98-21-245-4499; fax: +98-21-245-6845.
E-mail address: email@example.com (M.R. Safarinejad).
Journal of Diabetes and Its Complications 18 (2004) 205–210
four (2.7%) developed new chest pain within 2 h after
taking the drug. Two of them were admitted to CCU due to
acute myocardial infarction. Of four patients with new-onset
chest pain, one had controlled hypertension and one had
hypercholesterolemia. In this study, treatment with sildenafil
was well tolerated, but the safety profile of this drug in
patients with diabetes was not reassuring. The most common
adverse events associated with sildenafil treatment were
headache, flushing, dyspnea, and rhinitis. These were pre-
dominantly transient and moderate in nature. The incidence
of cardiovascular events were significantly much higher
(P<.001) in the patients taking sildenafil compared with
patients taking placebo. Given the chronic complications
associated with diabetes and because of a degree of risks
associated with sexual activity, physicians should inform
their patients before initiating sildenafil. The absence of a
previous history of coronary artery disease and a normal
standard 12-lead electrocardiogram do not necessarily imply
normal coronary arteries. In analyses of various subgroups of
patients with ED and diabetes, the efficacy of sildenafil was
not affected by patient age, the duration of diabetes, or the
duration of ED. The results for patients with Type 1 diabetes
were similar to those for patients with Type 2 diabetes. None
of them were smokers. Two patients discontinued treatment
with sildenafil due to severe headache.
The exact pathogenesis of ED in men with diabetes is not
well known. Improved erectile function in patients with
diabetes with sildenafil suggests that the production of cyclic
guanosine monophosphate remains at least partially intact in
diabetics. Whether or not nitric oxide and cyclic guanosine
monophosphate production are impaired in diabetes, further
studies are needed in animal models of diabetes.
In conclusion, oral sildenafil represents a moderately
effective treatment of organic ED in diabetic men. However,
therapy with this drug may causes serious cardiovascular
side effects in these patients.
We thank Mrs. Nayyer Shafiei Fazel for secretarial
assistance, Dr. A. A. Kolahi for statistical analysis, and Dr.
M. H. Ziraksaz for help in the running of study.
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