Cardiovascular Diseases, Stage B Heart Failure, Type 2 Diabetes Mellitus (T2DM)
Conditions
Keywords
SGLT2 Inhibitor, GLP-1 Receptor Agonist, Cardiovascular Protection, Artificial Intelligence Electrocardiography, AI-ECG, Global Longitudinal Strain, Diabetic Cardiomyopathy, Stage B Heart Failure, Pre-Heart Failure, OMOP Common Data Model, Real-World Data
Brief summary
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.
Detailed description
This is an investigator-initiated, two-phase observational study integrating a multicenter retrospective cohort analysis with a single-center prospective validation cohort. The two phases involve different study populations and data sources and will be analyzed independently. Their findings will be interpreted together to provide complementary evidence regarding long-term clinical cardiovascular outcomes and short-term changes in cardiac function among Korean patients with type 2 diabetes. In Phase 1, de-identified electronic health record data mapped to the Observational Medical Outcomes Partnership Common Data Model will be obtained from participating Korean hospitals through a distributed data network. A new-user, active-comparator cohort design will be used to compare patients initiating an SGLT2 inhibitor with those initiating a GLP-1 receptor agonist. Medication exposure, cardiovascular events, safety outcomes, metabolic measures, and treatment patterns will be identified using prespecified common data model definitions. Confounding will be addressed using propensity score methods, stratified analyses, and sensitivity analyses. Participating institutions will execute a common analytic protocol locally and provide only aggregated, non-identifiable results for multicenter analysis. In Phase 2, adults with type 2 diabetes who are scheduled to start an SGLT2 inhibitor during routine clinical care at Dongtan Sacred Heart Hospital will be consecutively screened. Baseline assessments will include standard 12-lead electrocardiography, portable 6-lead electrocardiography, AI-based ECG analysis, advanced echocardiography, laboratory testing, body composition assessment, and research blood sampling. Participants will be classified according to prespecified echocardiographic criteria for stage B heart failure. Approximately 50 participants who meet the protocol-defined criteria for the longitudinal cohort will undergo repeat assessments 6 months after baseline. Baseline data from other consented screening participants may be included in cross-sectional analyses. Phase 2 will evaluate whether AI-based ECG measurements reflect echocardiographic cardiac dysfunction at baseline and whether changes in AI-based ECG measurements correspond to changes in cardiac function after SGLT2 inhibitor treatment. Analyses will focus on changes within participants, correlations and agreement between AI-ECG and echocardiographic measurements, and the feasibility of AI-ECG for monitoring subclinical cardiac dysfunction. Medication selection, dose, continuation, and modification are determined solely by the treating physicians according to routine clinical practice. The protocol does not assign treatment, require medication changes, or use AI-ECG results to guide clinical care. No individual-level data will be combined across Phase 1 and Phase 2.
Interventions
None listed
Sponsors
Dongtan Sacred Heart Hospital
Chong Kun Dang Pharmaceutical Corp.
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Atherosclerotic Cardiovascular Disease Composite Event | From the index date until the first occurrence of acute myocardial infarction or ischemic stroke, loss to follow-up, death, or the end of available database records, whichever occurs first, assessed up to 12 years | Time from the index date to the first occurrence of acute myocardial infarction or ischemic stroke, identified using prespecified OMOP Common Data Model phenotype definitions. The outcome will be compared between treatment cohorts using hazard ratios with 95% confidence intervals. |
| Time to First Hospitalization for Heart Failure | From the index date until the first hospitalization for heart failure, loss to follow-up, death, or the end of available database records, whichever occurs first, assessed up to 12 years | Time from the index date to the first hospitalization accompanied by a diagnosis of heart failure, identified using prespecified OMOP Common Data Model phenotype definitions. The outcome will be compared between treatment cohorts using hazard ratios with 95% confidence intervals. |
| Change in Echocardiographic Global Longitudinal Strain | Baseline and 6 months after SGLT2 inhibitor initiation | Change in signed left ventricular global longitudinal strain from baseline to 6 months, calculated as GLS at 6 months minus GLS at baseline. A more negative change indicates improvement in left ventricular systolic function. |
Countries
South Korea
Contacts
CONTACTHun Jee Choe, MD, PhD
PRINCIPAL_INVESTIGATOREun-Gyoung Hong, MD, PhD
Hallym University Dongtan Sacred Heart Hospital
STUDY_DIRECTORHun Jee Choe
Hallym University Dongtan Sacred Heart Hospital
Outcome results
None listed