Association Between Diastolic Dysfunction and Erectile Dysfunction and the Effect of Tadalafil and SGLT2 Inhibitors on Them in Men With Metabolic Syndrome

This is a prospective, randomized, allocation-concealed, assessor-blinded, parallel-group clinical trial conducted at the Faculty of Medicine, Kafrelsheikh University. The study investigates the association between erectile dysfunction (ED) and left ventricular diastolic dysfunction (LVDD) in men with metabolic syndrome, and evaluates the effects of different treatment strategies on both conditions.

A total of 60 male patients aged 41 to 73 years diagnosed with metabolic syndrome and erectile dysfunction will be enrolled and randomly assigned into three parallel groups (1:1:1). The first group will receive tadalafil 5 mg once daily, the second group will receive an SGLT2 inhibitor (dapagliflozin or empagliflozin 10 mg once daily), and the third group will receive a combination of both treatments. The duration of intervention is 3 months.

Randomization will be performed using permuted block randomization, with allocation concealment ensured by an independent sequence holder. Outcome assessors will be blinded to treatment allocation.

Baseline and follow-up assessments will include clinical evaluation, metabolic parameters, echocardiographic assessment of left ventricular diastolic function, and evaluation of erectile function using the International Index of Erectile Function (IIEF).

The primary outcome is the change in erectile function as assessed by IIEF score after 3 months of treatment. Secondary outcomes include changes in echocardiographic parameters of diastolic function, correlation between erectile function and diastolic dysfunction, and identification of predictors of improvement in erectile function.

The study aims to provide insight into the relationship between cardiovascular dysfunction and erectile dysfunction in patients with metabolic syndrome and to determine whether combined therapy offers additional benefits over monotherapy.

Inclusion criteria

• Male patients aged ≥18 years
• History of sexual activity within the past 6 months
• Erectile dysfunction for at least 3 months (defined as IIEF-6 score ≤25)
• Diagnosed with metabolic syndrome

Exclusion criteria

• * Left ventricular systolic dysfunction (EF less than 50%)

• Recent myocardial infarction (within 1 month)
• Moderate to severe valvular heart disease (stenosis or regurgitation)
• Renal failure (eGFR <20 ml/min)
• Major pelvic surgery
• Significant central nervous system injury (e.g., spinal cord injury)
• Endocrine disorders (hypothyroidism, hypogonadism)
• Premature ejaculation
• Current balanitis or urogenital infections
• History of orthostatic hypotension
• Any contraindications to tadalafil or SGLT2 inhibitors