Moderate-intensity Statin vs. Individualized LDL-C Target-based Therapy in Older Adults With Type 2 Diabetes (iTARGET-Elderly Study)

• Moderate-intensity statin monotherapy (Drug): 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.
• Ezetimibe or ezetimibe-statin combination therapy (Drug): 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.

Primary outcomes

• 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 outcomes

• 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, adverse drug reactions, and serious adverse events [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

Sex: All, ages: 70 Years to any

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

• Sin Gon Kim, MD, Principal investigator, Korea University Anam Hospital
• Bong-Soo Cha, MD, Principal investigator, Severance Hospital