Dyslipidemia Associated With Type II Diabetes Mellitus
Conditions
Keywords
Dyslipidemia, T2D, Diabetes, Statins, iTARGET-Elderly, RRCT
Brief summary
Statins are the cornerstone of cardiovascular disease (CVD) prevention through the lowering of low-density lipoprotein cholesterol (LDL-C). While the benefits of intensive LDL-C lowering are well-established for secondary prevention, evidence remains insufficient for primary prevention in the elderly-specifically for individuals aged 70 years or older with type 2 diabetes who have no prior history of atherosclerotic cardiovascular events. Current guidelines generally recommend moderate-intensity statins for this population based on extrapolated data. However, there is a significant evidence gap regarding whether these older adults, who have not yet experienced a cardiovascular event, derive the same risk-benefit ratio from pharmacological intervention as younger or secondary prevention groups. Furthermore, while ezetimibe (alone or in combination) is an effective alternative for patients with established disease, its efficacy as a primary prevention strategy in older diabetic patients has not been rigorously confirmed through randomized controlled trials (RCTs). Therefore, this study specifically focuses on the primary prevention setting, aiming to determine whether individualized LDL-C target-based therapy is non-inferior to standard moderate-intensity statin therapy in preventing first-time cardiovascular events among older patients with type 2 diabetes.
Interventions
DRUGModerate-intensity statin monotherapy
Atorvastatin 10 mg, 20 mg, or 40 mg, or rosuvastatin 5 mg, 10 mg, or 20 mg will be administered for up to 3 years. If the LDL-C is ≥100 mg/dL, the investigator may adjust the statin intensity based on the patient's health status.
DRUGEzetimibe or ezetimibe-statin combination therapy
Treatment will consist of non-pharmacological interventions or marketed medications, including low-dose statins (atorvastatin 5 mg or 10 mg, rosuvastatin 2.5 mg or 5 mg) in combination with ezetimibe 10 mg, or fixed-dose combinations (rosuvamibe 10/2.5 mg, atorvabmibe 10/5 mg, or Rosuzet 10/2.5 mg), for up to 3 years. If the pre-specified LDL-C target is not achieved or drug intolerance occurs, adjustments in dosage or medication will be made.
Sponsors
Sin Gon Kim
Severance Hospital
Hanmi Pharmaceutical Company Limited
Yuhan Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Eligible patients will be randomly assigned in a 1:1 ratio at Visit 1, using the Interactive Web Response System (IWRS), to either the moderate-intensity statin monotherapy arm or the individualized LDL-C target-based therapy arm.
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provision of written informed consent to participate in the study by the patient or his/her legally authorized representative after receiving and understanding a detailed explanation of the study * Adults aged 70 years or older * Diagnosed with type 2 diabetes or currently receiving antidiabetic medication, without a history or presence of cardiovascular disease * Either: (1) LDL-C≥100 mg/dL if not receiving lipid-lowering therapy, or (2) currently receiving lipid-lowering therapy (in this case, LDL-C level not restricted)
Exclusion criteria
* Diagnosis of type 1 diabetes * Documented history of atherosclerotic cardiovascular disease at screening, confirmed clinically or by imaging: (1) myocardial infarction; (2) coronary revascularization; (3) currently receiving treatment for acute coronary syndrome; (4) history of ischemic stroke; (5) aortic aneurysm; (6) peripheral arterial disease * Currently undergoing cancer treatment * Severe disease requiring recurrent hospitalization * Frailty (defined as a score ≥3 on the Korean FRAIL questionnaire), or any condition significantly limiting self-care * AST or ALT \>3 × ULN, at screening (however, patients will be eligible if repeat testing at the time of randomization shows levels \<3 × ULN), or liver cirrhosis * Contraindications to study drugs * Pregnant or breastfeeding women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time from the date of randomization to the first occurrence of a major adverse cardiovascular event (MACE) | 0, 3, 12, 24, 36 months | Major adverse cardiovascular event (MACE) includes death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke, hospitalization due to heart failure, coronary revascularization, or all-cause death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time from the date of randomization to the first hospitalization due to the following events or to the first occurrence of such events, whichever occurs earlier : (1) ischemic heart disease, (2) cerebrovascular disease, (3) heart failure, (4) peripheral | 0, 3, 12, 24, 36 months | — |
| Time from the date of randomization to the first occurrence of all-cause hospitalization or all-cause death, whichever occurs first | 0, 3, 12, 24, 36 months | — |
| Serum lipid levels from baseline at each assessment time point | 0, 3, 12, 24, 36 months | — |
| Serum lipid changes from baseline at each assessment time point | 0, 3, 12, 24, 36 months | — |
| Patterns of study drug use | From baseline up to 36 months | — |
| Incidence rates and characteristics of adverse events of special interest (AESI) | From baseline up to 36 months | Adverse events of special interest (AESI): (1) Elevation of aminotransferase levels, (2) Rhabdomyolysis/myopathy, (3) Gastrointestinal problems |
| Incidence rates and characteristics of adverse events, adverse drug reactions, and serious adverse events | From baseline up to 36 months | — |
Countries
South Korea
Contacts
CONTACTKim
PRINCIPAL_INVESTIGATORSin Gon Kim, MD
Korea University Anam Hospital
PRINCIPAL_INVESTIGATORBong-Soo Cha, MD
Severance Hospital
Outcome results
None listed