A new study finds that a popular erectile dysfunction drug, which is increasingly being used to try to prevent heart complications in people with type 2 diabetes, doesn’t benefit women with diabetes.
Only one previous randomized study examining the heart benefits of erectile dysfunction drug for patients with diabetes enrolled both men and women, and even that trial did not analyze the data by sex.
“Most of the cardiovascular studies published so far actually do not include women,” said Riccardo Pofi, a clinical research fellow at the University of Oxford who led this research while he was at Sapienza University of Rome. The problem is not merely a lack of sex-based differentiation in statistical analysis, but a lack of conceptualizing and designing studies to include women, he explained.
The clinical trial enrolled 122 middle-aged people — 65 men and 57 women — with long-term diabetes. Over the course of five months, half of the participants took daily oral tadalafil, also known by the brand name Cialis, while the other half took a placebo. Results were reported Wednesday in Science Translational Medicine.
Patients with diabetes develop stiffer and thicker heart muscles that make it difficult for muscle fibers to contract and circulate blood to the rest of the body. To compensate, the heart twists in patients with diabetes — essentially wringing itself out like a towel to expel blood.
This is where tadalafil, an inhibitor of a protein called PDE5, was shown to benefit men: After 20 weeks, men had reduced torsion — a measure of the heart’s twisting — and increased fiber shortening. The same benefits were not observed among enrolled women, who were all post-menopausal.
The benefits were elevated in men with higher testosterone and lower in women with low estrogen, so it is likely that sex hormones are part of the puzzle to improve diabetic cardiac function, the authors said.
Rakesh Kukreja, a professor of cardiology at Virginia Commonwealth University School of Medicine who was not involved with the study, said that two major gaps he would like to see addressed include biopsying heart tissue in women to ensure there is sufficient PDE5 expression for the drug to inhibit and assessing the role of estrogen supplementation.
The researchers plan to study the effect of tadalafil on premenopausal women as well as estrogen supplementation on those who are reaching menopause. The women would be given exogenous estrogen to see if it can help tadalafil work.
Andrea M. Isidori, a physician and professor of endocrinology at the Sapienza University of Rome and corresponding author on the paper, said a larger population study to track hospitalizations and deaths would also be useful.
Still, against a backdrop of previously conflicting studies about the role of PDE5 inhibitors on cardiac changes, Kukreja applauded the team’s clear demonstration that tadalafil restores normal contraction of the heart.
“This trial clarifies some major inconsistencies about the cardioprotective role of PDE5 inhibitors in type 2 diabetes in men and women,” Kukreja said.
All patients in the current trial were either white or of Asian ethnicity.
“The study is really pioneering in terms of methodology, approach, the tools that we use to diagnose diabetic cardiomyopathy, and all the molecular analysis of pathways that we have spotted,” Pofi said.
Easily accessible and affordable erectile dysfunction medications have potential to address heart and kidney complications associated with type 2 diabetes, but the authors said additional research is needed to continue clarifying their sex and tissue-specific targets.