Dual vs Triple Lipid-Lowering Therapy in Type 2 Diabetes Mellitus Patients With Elevated LDL Cholesterol

Bahria University

Status and phase: Not yet enrolling; Phase 4

Conditions: Type 2 Diabetes Mellitus; Hypercholesterolemia / Elevated LDL Cholesterol

Treatments: Drug: Bempedoic Acid + Ezetimibe; Drug: Rosuvastatin + Ezetimibe; Drug: Rosuvastatin + Ezetimibe + Bempedoic Acid

Study type: Interventional

Funder types: Other

Identifiers

NCT07255820

BUHS-IRB # 180/25

Details and patient eligibility

About

This Open-label, randomized clinical trial evaluates the comparative efficacy and safety of dual versus triple lipid-lowering therapy using rosuvastatin, ezetimibe, and bempedoic acid in patients with type 2 diabetes mellitus and elevated LDL cholesterol. The study aims to determine whether adding bempedoic acid to standard dual therapy provides superior lipid control without compromising safety. The 126 participants, aged 35 - 60 years will be randomly assigned to one of three treatment groups for 12 weeks, and their lipid profiles, glycemic control, and adverse effects will be monitored.The total duration of study will be 6 months, with a 3 months individual treatment period.

Full description

This is a single-center, randomized, open-label clinical trial conducted over a 12-week period to evaluate the comparative efficacy and safety of dual versus triple lipid-lowering therapy in patients with type 2 diabetes mellitus (T2DM) and elevated LDL cholesterol (LDL-C).

The trial includes three treatment arms, Arm A will receive Rosuvastatin + Ezetimibe, Arm B will receive Bempedoic Acid + Ezetimibe and Arm C will receive Rosuvastatin + Ezetimibe + Bempedoic Acid.

Eligible participants are adults aged 35 - 60 years with a confirmed diagnosis of type 2 diabetes mellitus and elevated LDL cholesterol despite standard care. Exclude patients with severe hepatic or renal impairment, history of gout or hyperuricemia, muscle disorders or previous statin intolerance or Participation in another clinical trial within 30 days All participants will be randomly assigned to one of the three arms. Baseline assessments include lipid profile (TC, TG, HDL, LDL, VLDL), glycemic parameters (FBS, RBS, HbA1c), creatine kinase, uric acid, and documentation of medical history and concomitant medications. Follow-up assessments will occur at week 12 to evaluate changes in primary and secondary outcomes.

The primary outcome is change in LDL cholesterol from baseline to 12 weeks and secondary Outcomes include total cholesterol (TC), high-density lipoprotein (HDL), triglycerides (TG), very-low-density lipoprotein (VLDL), creatine kinase (CK), Uric acid, glycemic control like HbA1c, fasting blood sugar (FBS), random blood sugar (RBS), safety and tolerability including muscle spasm, myalgia, or gout attacks Safety Monitoring through all adverse events will be recorded during the study. If participants reporting muscle symptoms or hyperuricemia will be evaluated promptly. Laboratory tests will be repeated at study completion or earlier if clinically indicated.

This study is designed to assess whether the addition of bempedoic acid to standard dual therapy provides superior lipid-lowering efficacy without increasing adverse events in T2DM patients with elevated LDL-C. The findings will inform clinical practice on optimal lipid-lowering strategies for high-risk diabetic patients.

The study has received approval from BUHS-IRB (#180/25) and will be conducted in accordance with Good Clinical Practice (GCP) guidelines. Written informed consent will be obtained from all participants before study procedures.

Enrollment: 126 estimated patients

Sex: All

Ages: 35 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Males and females Age 35-60 years HbA1c ≥ 7.0 (≥ 48 mmol/mol) On stable anti-diabetic therapy for at least 3 months LDL-C > 100 mg/dL on at least two occasions Diagnosed with hypercholesterolemia Establish high cardiovascular risk (e.g, previous MI, stroke or atherosclerosis) or

• 2 cardiovascular risk factors (hypertension, smoking, obesity, family history) BMI >23 - <32(WHO Asian Criteria) No prior statin side effects

Exclusion criteria

HbA1c >10 % (86 mmol/mol) BMI > 32 Type 1 Diabetes, gestational diabetes Pregnancy or lactation Acute liver disease or ALT/AST levels > 3× the upper limit of normal Renal failure (GFR < 30 mL/min) Uncontrolled hypothyroidism or nephrotic syndrome Recent cancer diagnosis (last 6 months) Current use of other lipid-lowering agents (e.g., fibrates or PCSK9 inhibitors) Known allergy to any component Statin intolerance with severe adverse effects (e.g., rhabdomyolysis)

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Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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126 participants in 3 patient groups

Rosuvastatin + Ezetimibe

Active Comparator group

Description:

Rosuvastatin is a statin that lowers LDL cholesterol by inhibiting HMG-CoA reductase. Ezetimibe inhibits cholesterol absorption in the intestine.

Treatment:

Drug: Rosuvastatin + Ezetimibe

Bempedoic Acid + Ezetimibe

Active Comparator group

Description:

Bempedoic acid is an ATP citrate lyase inhibitor that reduces LDL cholesterol. Ezetimibe inhibits diatery cholesterol absorption in the intestine

Treatment:

Drug: Bempedoic Acid + Ezetimibe

Rosuvastatin + Ezetimibe + Bempedoic Acid

Active Comparator group

Description:

This triple therapy combines statin therapy with cholesterol absorption inhibition and ATP citrate lyase inhibition to optimize LDL reduction.

Treatment:

Drug: Rosuvastatin + Ezetimibe + Bempedoic Acid