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

A Randomized, Allocation-concealed, Assessor-blinded, Parallel-group Trial Evaluating the Association Between Erectile Dysfunction and Left Ventricular Diastolic Dysfunction and Comparing the Effects of Tadalafil, SGLT2 Inhibitors, and Their Combination in Patients With Metabolic Syndrome.

Metabolic syndrome is associated with an increased risk of cardiovascular disease and is commonly accompanied by erectile dysfunction and subclinical cardiac dysfunction. Erectile dysfunction and left ventricular diastolic dysfunction may share common underlying mechanisms, including endothelial dysfunction and microvascular impairment.

This study aims to investigate the association between erectile dysfunction and left ventricular diastolic dysfunction in men with metabolic syndrome, and to evaluate the effects of different treatment strategies, including tadalafil and SGLT2 inhibitors, on both erectile function and cardiac diastolic function.

Participants will be randomly assigned to receive tadalafil, an SGLT2 inhibitor, or a combination of both for a duration of three months. Clinical, echocardiographic, and functional assessments will be performed at baseline and after treatment.

The results of this study may improve understanding of the link between cardiovascular and sexual dysfunction and help guide therapeutic approaches in this patient population.

Study Overview

• Status: Completed
• Conditions: Metabolic Syndrome; Erectile Dysfunction; Left Ventricular Diastolic Dysfunction
• Intervention / Treatment: Drug: Tadalafil 5 mg; Drug: SGLT-2 inhibitor; Drug: Tadalafil plus SGLT2 inhibitors

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Kafrelsheikh Governrate
    • Kafr ash Shaykh, Kafrelsheikh Governrate, Egypt, 33511
      • Kafrelsheikh univeristy hospital, Faculty of medicine, Kafrelsheikh univeristy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tadalafil Group; Participants received tadalafil 5 mg orally once daily for 3 months. Erectile function, left ventricular diastolic function, and metabolic parameters were assessed at baseline and after completion of treatment.	Drug: Tadalafil 5 mg; Tadalafil 5 mg once daily for three months
Experimental: SGLT2 inhibitors group; Participants received SGLT2 inhibitors (dapagliflozin or empagliflozin) 10 mg orally once daily for 3 months. Erectile function, left ventricular diastolic function, and metabolic parameters were assessed at baseline and after completion of treatment.	Drug: SGLT-2 inhibitor; SGLT2 inhibitors 10 mg orally once daily for three months; Other Names: Dapagliflozin; Empagliflozin
Experimental: Combination therapy; Participants received combination therapy with tadalafil 5 mg once daily plus SGLT2 inhibitors 10 mg once daily for 3 months. Erectile function, left ventricular diastolic function, and metabolic parameters were assessed at baseline and after completion of treatment.	Drug: Tadalafil plus SGLT2 inhibitors; Combination therapy with tadalafil 5 mg once daily and SGLT2 inhibitors 10 mg once daily for three months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in erectile function assessed by the International Index of Erectile Function (IIEF)	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.	Baseline and 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in left ventricular diastolic function assessed by echocardiographic parameters	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.	Baseline and 3 months
Correlation between changes in IIEF score and echocardiographic parameters	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).	Baseline and 3 months
Predictors of change in IIEF score	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).	Baseline and 3 months

Collaborators and Investigators

• Sponsor: Kafrelsheikh University
• Investigators: Study Chair: Reda B Bastawisy, MD (Professor), Faculty of medicine, Kafrelshiekh university; Study Chair: Wael A Haseeb, MD (Assistant professor), Faculty of medicine, Kafrelshiekh university; Study Chair: Mohamed G Abdelraouf, MD, Faculty of medicine, Kafrelshiekh university

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2025
• Primary Completion (Actual): March 17, 2026
• Study Completion (Actual): March 17, 2026

Study Registration Dates

• First Submitted: April 21, 2026
• First Submitted That Met QC Criteria: April 29, 2026
• First Posted (Actual): May 4, 2026

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Endothelial dysfunction; Cardiovascular risk; Echocardiography; SGLT2 inhibitors; Tadalafil; Diastolic function
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Cardiovascular Diseases; Mental Disorders; Genital Diseases, Male; Male Urogenital Diseases; Heart Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Insulin Resistance; Hyperinsulinism; Ventricular Dysfunction; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological; Nutritional and Metabolic Diseases; Metabolic Syndrome; Ventricular Dysfunction, Left; Erectile Dysfunction; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmacologic Actions; Chemical Actions and Uses; Indoles; Indole Alkaloids; Heterocyclic Compounds, 3-Ring; Carbolines; Tadalafil; Sodium-Glucose Transporter 2 Inhibitors; empagliflozin; dapagliflozin
• Other Study ID Numbers: METDDED-01; PACTR202604903325533 (Registry Identifier: Pan African Clinical Trials Registry (PACTR))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (including baseline characteristics, outcome measures, and relevant clinical variables) will be made available upon reasonable request after publication of the study results.
• IPD Sharing Time Frame: Data will be available starting 6 months after publication and will remain available for up to 2 years.
• IPD Sharing Access Criteria: Access will be granted to qualified researchers upon reasonable request, subject to approval by the principal investigator and institutional ethics committee, and after signing a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No