Cardioprotective Effects of SGLT2 Inhibitors and GLP-1 Receptor Agonists in Korean Patients With Type 2 Diabetes

Evaluation of Cardioprotective Effects of SGLT2 Inhibitors and GLP-1 Receptor Agonists in Korean Patients With Type 2 Diabetes: A Multicenter CDM-Based Retrospective Cohort Study With Prospective AI-ECG Validation

This observational study will evaluate the cardiovascular effects of sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) and glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists) in Korean adults with type 2 diabetes.

The study consists of two phases. Phase 1 will use de-identified electronic health record data from multiple Korean hospitals organized in a common data model. Cardiovascular outcomes, including myocardial infarction, ischemic stroke, and hospitalization for heart failure, will be compared among patients who started an SGLT2 inhibitor or a GLP-1 receptor agonist. Fractures, metabolic changes, and real-world medication use will also be evaluated.

Phase 2 will prospectively enroll approximately 100 adults with type 2 diabetes who are starting an SGLT2 inhibitor as part of routine clinical care at Dongtan Sacred Heart Hospital. Participants will undergo electrocardiography, AI-based ECG analysis, echocardiography, blood and urine tests, and body composition assessment at baseline. Approximately 50 participants with stage B heart failure, defined as structural or functional heart abnormalities without heart failure symptoms, will undergo the same assessments after 6 months. The primary outcome of Phase 2 is the change in echocardiographic global longitudinal strain from baseline to 6 months. The study will also examine whether changes detected by AI-based ECG are associated with changes in echocardiographic measures of cardiac function.

The study does not assign medications or alter routine treatment. All treatment decisions are made by the participants' treating physicians.

Phase 1: Retrospective Cohorts

Inclusion Criteria:

• Adults aged 19 years or older.
• Diagnosis of type 2 diabetes mellitus.
• New initiation of a study medication, including an SGLT2 inhibitor, a GLP-1 receptor agonist, or another eligible glucose-lowering medication.
• At least 180 days of observable data before the index date, defined as the date of the first eligible prescription.

Exclusion Criteria:

• Type 1 diabetes mellitus or secondary diabetes mellitus.
• Use of a medication from the same drug class within 90 days before the index date.
• Pregnancy recorded during the relevant study period.
• A history of the outcome being evaluated during the baseline period, applied separately for each outcome analysis.

Phase 2: Prospective SGLT2 Inhibitor Validation Cohort

Inclusion Criteria:

• Adults aged 50 years or older receiving outpatient care at Dongtan Sacred Heart Hospital.
• Diagnosis of type 2 diabetes mellitus.
• No current or previous signs or symptoms of heart failure and New York Heart Association functional class I.
• At least one of the following high-risk characteristics: diabetes duration of 5 years or longer, hypertension, body mass index of 25 kg/m² or higher, urinary albumin-to-creatinine ratio of 30 mg/g or higher, estimated glomerular filtration rate below 60 mL/min/1.73 m², or diabetic microvascular complications.
• No previous treatment with an SGLT2 inhibitor and scheduled to initiate an SGLT2 inhibitor based on the treating physician's clinical judgment.
• Ability and willingness to provide written informed consent.

Exclusion Criteria:

• Current or previous diagnosis of heart failure, hospitalization for heart failure, clinically suspected signs or symptoms of heart failure, or screening left ventricular ejection fraction below 50%.
• Moderate or severe valvular heart disease, known hypertrophic, dilated, or infiltrative cardiomyopathy, complex congenital heart disease, or clinically significant pericardial disease.
• Acute coronary syndrome, coronary revascularization, or stroke within 3 months before enrollment.
• Presence of a pacemaker, implantable cardioverter-defibrillator, or cardiac resynchronization therapy device.
• Atrial fibrillation, sustained tachycardia, frequent premature contractions, or another arrhythmia that prevents reliable comparison of ECG or global longitudinal strain measurements.
• Type 1 diabetes mellitus, secondary diabetes mellitus, diabetic ketoacidosis within the previous year, or another clinical condition making SGLT2 inhibitor treatment inappropriate.
• Estimated glomerular filtration rate below 30 mL/min/1.73 m² or dialysis.
• Echocardiographic image quality insufficient for reliable 3-view global longitudinal strain or stage B heart failure assessment.
• Pregnancy or breastfeeding.
• Unwillingness to undergo study assessments or inability to complete the 6-month follow-up.