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.

• Tadalafil 5 mg (Drug): Tadalafil 5 mg once daily for three months
• SGLT-2 inhibitor (Drug), also known as Dapagliflozin, Empagliflozin: SGLT2 inhibitors 10 mg orally once daily for three months
• Tadalafil plus SGLT2 inhibitors (Drug): Combination therapy with tadalafil 5 mg once daily and SGLT2 inhibitors 10 mg once daily for three months

Primary outcomes

• Change in erectile function assessed by the International Index of Erectile Function (IIEF) [Baseline and 3 months]: Change in erectile function assessed by the International Index of Erectile Function (IIEF-6). The IIEF-6 is a validated questionnaire with scores ranging from 1 to 30, where higher scores indicate better erectile function. The outcome measure will be the change in IIEF-6 score from baseline to 3 months after treatment.

Secondary outcomes

• Change in left ventricular diastolic function assessed by echocardiographic parameters [Baseline and 3 months]: Left ventricular diastolic function will be assessed using specific echocardiographic parameters in accordance with ASE/EACVI guidelines, including E/e' ratio, isovolumic relaxation time (IVRT, ms), deceleration time (DT, ms), and pulmonary artery systolic pressure (PASP, mmHg). Each parameter will be measured at baseline and at 3 months, and analyzed individually as components of overall diastolic function to evaluate changes over time.
• Correlation between changes in IIEF score and echocardiographic parameters [Baseline and 3 months]: Correlation between changes in erectile function assessed by the International Index of Erectile Function (IIEF-6) score (range: 1-30, higher scores indicate better erectile function) and changes in selected echocardiographic parameters of left ventricular diastolic function, including E/e' ratio, isovolumic relaxation time (IVRT, ms), deceleration time (DT, ms), and pulmonary artery systolic pressure (PASP, mmHg).
• Predictors of change in IIEF score [Baseline and 3 months]: Identification of independent predictors of change in erectile function assessed by the International Index of Erectile Function (IIEF-6) score (range: 1-30, higher scores indicate better erectile function). Predictors include selected clinical variables (age, years; smoking status, categorical), metabolic parameters (waist circumference, cm; systolic and diastolic blood pressure, mmHg; fasting blood glucose, mg/dL; HDL cholesterol, mg/dL; triglycerides, mg/dL), and specific echocardiographic parameters (E/e' ratio, unitless; isovolumic relaxation time \[IVRT\], ms; deceleration time \[DT\], ms; pulmonary artery systolic pressure \[PASP\], mmHg).

Sex: Male, ages: 18 Years to any

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

• Reda B Bastawisy, MD (Professor), Study chair, Faculty of medicine, Kafrelshiekh university
• Wael A Haseeb, MD (Assistant professor), Study chair, Faculty of medicine, Kafrelshiekh university
• Mohamed G Abdelraouf, MD, Study chair, Faculty of medicine, Kafrelshiekh university