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

NCT ID: NCT07255820

Last Updated: 2025-12-01

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 126 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-01
• Study Completion Date: 2026-06-30

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.

Conditions

Type 2 Diabetes Mellitus; Hypercholesterolemia / Elevated LDL Cholesterol

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rosuvastatin + Ezetimibe

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

Group Type: ACTIVE_COMPARATOR

Rosuvastatin + Ezetimibe

Intervention Type: DRUG

Group A (Dual therapy 1): Tab Rosuvastatin 20 mg + Tab Ezetimibe 10mg (FDC) orally, once daily for 90 days

Bempedoic Acid + Ezetimibe

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

Group Type: ACTIVE_COMPARATOR

Bempedoic Acid + Ezetimibe

Intervention Type: DRUG

Group B (Dual therapy 2): Tab Bempedoic Acid 180mg+ Tab Ezetimibe 10mg (FDC) orally, once daily for 90 days

Rosuvastatin + Ezetimibe + Bempedoic Acid

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

Group Type: ACTIVE_COMPARATOR

Rosuvastatin + Ezetimibe + Bempedoic Acid

Intervention Type: DRUG

Group C (Triple therapy): Tab Rosuvastatin 20 mg+ Tab Ezetimibe 10mg+ Tab Bempedoic Acid 180mg orally, once daily for 90 days

Interventions

Rosuvastatin + Ezetimibe

Group A (Dual therapy 1): Tab Rosuvastatin 20 mg + Tab Ezetimibe 10mg (FDC) orally, once daily for 90 days

Intervention Type: DRUG

Bempedoic Acid + Ezetimibe

Group B (Dual therapy 2): Tab Bempedoic Acid 180mg+ Tab Ezetimibe 10mg (FDC) orally, once daily for 90 days

Intervention Type: DRUG

Rosuvastatin + Ezetimibe + Bempedoic Acid

Group C (Triple therapy): Tab Rosuvastatin 20 mg+ Tab Ezetimibe 10mg+ Tab Bempedoic Acid 180mg orally, once daily for 90 days

Intervention Type: DRUG

Eligibility Criteria

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)

-

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bahria University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fatima Khatoon, MBBS

Role: PRINCIPAL_INVESTIGATOR

Bahria University, Islamabad

Locations

National Medical Center

Karachi, Sindh, Pakistan

Countries

Pakistan

Central Contacts

Fatima Khatoon, MBBS

Role: CONTACT

fatima.omair@gmail.com

+923213334507

Ijaz Hussain Zaidi, MBBS, MPHIL, PHD, POST-DOC

Role: CONTACT

syedijaz.bumdc@bahria.edu.pk

+923212794282

Facility Contacts

Dr. Muhammad Sajid Abbas Jaffri, MBBS, MCPS, FCPS,

Role: primary

muhammadsajidjaffri@gmail.com

+923002139364

Fatima Khatoon, MBBS

Role: backup

fatima.omair@gmail.com

+923213334507

References

Laufs U, Ballantyne CM, Banach M, Bays H, Catapano AL, Duell PB, Goldberg AC, Gotto AM, Leiter LA, Ray KK, Bloedon LT, MacDougall D, Zhang Y, Mancini GBJ. Efficacy and safety of bempedoic acid in patients not receiving statins in phase 3 clinical trials. J Clin Lipidol. 2022 May-Jun;16(3):286-297. doi: 10.1016/j.jacl.2022.03.001. Epub 2022 Mar 13.

Reference Type: BACKGROUND

PMID: 35346603 (View on PubMed)

Rubino J, MacDougall DE, Sterling LR, Hanselman JC, Nicholls SJ. Combination of bempedoic acid, ezetimibe, and atorvastatin in patients with hypercholesterolemia: A randomized clinical trial. Atherosclerosis. 2021 Mar;320:122-128. doi: 10.1016/j.atherosclerosis.2020.12.023. Epub 2020 Dec 31.

Reference Type: BACKGROUND

PMID: 33514449 (View on PubMed)

Ballantyne CM, Laufs U, Ray KK, Leiter LA, Bays HE, Goldberg AC, Stroes ES, MacDougall D, Zhao X, Catapano AL. Bempedoic acid plus ezetimibe fixed-dose combination in patients with hypercholesterolemia and high CVD risk treated with maximally tolerated statin therapy. Eur J Prev Cardiol. 2020 Apr;27(6):593-603. doi: 10.1177/2047487319864671. Epub 2019 Jul 29.

Reference Type: BACKGROUND

PMID: 31357887 (View on PubMed)

Goldberg AC, Leiter LA, Stroes ESG, Baum SJ, Hanselman JC, Bloedon LT, Lalwani ND, Patel PM, Zhao X, Duell PB. Effect of Bempedoic Acid vs Placebo Added to Maximally Tolerated Statins on Low-Density Lipoprotein Cholesterol in Patients at High Risk for Cardiovascular Disease: The CLEAR Wisdom Randomized Clinical Trial. JAMA. 2019 Nov 12;322(18):1780-1788. doi: 10.1001/jama.2019.16585.

Reference Type: BACKGROUND

PMID: 31714986 (View on PubMed)

Bays HE, Banach M, Catapano AL, Duell PB, Gotto AM Jr, Laufs U, Leiter LA, Mancini GBJ, Ray KK, Bloedon LT, Sasiela WJ, Ye Z, Ballantyne CM. Bempedoic acid safety analysis: Pooled data from four phase 3 clinical trials. J Clin Lipidol. 2020 Sep-Oct;14(5):649-659.e6. doi: 10.1016/j.jacl.2020.08.009. Epub 2020 Sep 2.

Reference Type: BACKGROUND

PMID: 32980290 (View on PubMed)

Pirillo A, Catapano AL. New insights into the role of bempedoic acid and ezetimibe in the treatment of hypercholesterolemia. Curr Opin Endocrinol Diabetes Obes. 2022 Apr 1;29(2):161-166. doi: 10.1097/MED.0000000000000706.

Reference Type: BACKGROUND

PMID: 34980867 (View on PubMed)

Nissen SE, Lincoff AM, Brennan D, Ray KK, Mason D, Kastelein JJP, Thompson PD, Libby P, Cho L, Plutzky J, Bays HE, Moriarty PM, Menon V, Grobbee DE, Louie MJ, Chen CF, Li N, Bloedon L, Robinson P, Horner M, Sasiela WJ, McCluskey J, Davey D, Fajardo-Campos P, Petrovic P, Fedacko J, Zmuda W, Lukyanov Y, Nicholls SJ; CLEAR Outcomes Investigators. Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients. N Engl J Med. 2023 Apr 13;388(15):1353-1364. doi: 10.1056/NEJMoa2215024. Epub 2023 Mar 4.

Reference Type: BACKGROUND

PMID: 36876740 (View on PubMed)

Marazzi G, Caminiti G, Perrone MA, Campolongo G, Cacciotti L, Giamundo DM, Iellamo F, Severino P, Volterrani M, Rosano G. Addition of Bempedoic Acid to Statin-Ezetimibe versus Statin Titration in Patients with High Cardiovascular Risk: A Single-Centre Prospective Study. J Cardiovasc Dev Dis. 2024 Sep 14;11(9):286. doi: 10.3390/jcdd11090286.

Reference Type: BACKGROUND

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Related Links

https://www.acc.org/latest-in-cardiology

ACC/AHA cholesterol management guidelines

https://www.diabetes.org/

ADA information on diabetes and cardiovascular risk.

Other Identifiers

BUHS-IRB # 180/25

Identifier Type: -

Identifier Source: org_study_id