Hypercholesterolemia / Elevated LDL Cholesterol, Type 2 Diabetes Mellitus
Conditions
Keywords
Lipid-lowering therapy,, Rosuvastatin, Ezetimibe, Bempedoic Acid, Dual therapy vs Triple therapy, LDL-C, Dyslipidemia, Type 2 Diabetes
Brief summary
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.
Detailed 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.
Interventions
DRUGRosuvastatin + Ezetimibe
Group A (Dual therapy 1): Tab Rosuvastatin 20 mg + Tab Ezetimibe 10mg (FDC) orally, once daily for 90 days
DRUGBempedoic Acid + Ezetimibe
Group B (Dual therapy 2): Tab Bempedoic Acid 180mg+ Tab Ezetimibe 10mg (FDC) orally, once daily for 90 days
DRUGRosuvastatin + Ezetimibe + Bempedoic Acid
Group C (Triple therapy): Tab Rosuvastatin 20 mg+ Tab Ezetimibe 10mg+ Tab Bempedoic Acid 180mg orally, once daily for 90 days
Sponsors
Bahria University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
35 Years to 60 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary outcome: Percent Change in LDL-C From Baseline to 12 Weeks and Proportion of Participants Achieving LDL-C <70 mg/dL | 12 weeks | The study will measure the percent change in LDL-C from baseline to 12 weeks and the proportion of participants achieving LDL-C \<70 mg/dL as per international guidelines. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary outcome : Change in Total Cholesterol Level From Baseline to 12 Weeks (mg/dL) | 12 weeks | The study will measure the change in total cholesterol (mg/dL) from baseline to 12 weeks to evaluate the efficacy of dual and triple lipid-lowering therapies. |
| Secondary Outcome : Change in Triglyceride Level From Baseline to 12 Weeks (mg/dL) | 12 weeks | The study will measure the change in Triglyceride Level from baseline to 12 weeks to evaluate the efficacy of dual and triple lipid-lowering therapies. |
| Secondary Outcome : Change in HDL-C Level From Baseline to 12 Weeks (mg/dL) | 12 weeks | The study will measure the change in HDL-C Level from baseline to 12 weeks to evaluate the efficacy of dual and triple lipid-lowering therapies. |
| Secondary Outcome : Change in VLDL Level From Baseline to 12 Weeks (mg/dL) | 12 weeks | The study will measure the change in VLDL Level from baseline to 12 weeks to evaluate the efficacy of dual and triple lipid-lowering therapies. |
| Secondary Outcome (Safety - Muscle Marker): Change in Creatine Kinase (CK) Level From Baseline to 12 Weeks (U/L) | 12 weeks | The study will monitor creatine kinase levels from baseline to 12 weeks to assess muscle-related safety of the therapies |
| Secondary Outcome (Safety - Metabolic Marker): Change in Uric Acid Level From Baseline to 12 Weeks (mg/dL) | 12 weeks | The study will monitor uric acid levels from baseline to 12 weeks to assess the metabolic safety of the therapies. |
| Secondary Outcome (Adverse Events): Number of Participants Experiencing Treatment-Related Adverse Effects | 12 weeks | The study will record any treatment-related adverse effects (e.g., muscle spasm, gout, gastrointestinal symptoms) over 12 weeks to assess overall safety. |
Countries
Pakistan
Contacts
PRINCIPAL_INVESTIGATORFatima Khatoon, MBBS
Bahria University, Islamabad
Outcome results
None listed