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

NCT07255820 | Not Yet Recruiting Phase 4

• 1 other identifier: BUHS-IRB # 180/25
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 2 Diabetes Mellitus; Hypercholesterolemia / Elevated LDL Cholesterol

Keywords

Lipid-lowering therapy,; Rosuvastatin, Ezetimibe, Bempedoic Acid; Dual therapy vs Triple therapy; LDL-C; Dyslipidemia; Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Primary outcome: Percent reduction in LDL-C and proportion of patients achieving LDL-C <70 mg/dL

  The study will measure the percentage change in LDL-C from baseline to 12 weeks and the proportion of participants achieving LDL-C \<70 mg/dL as per international guidelines to assess the efficacy of dual and triple lipid-lowering therapies in patients with Type 2 Diabetes Mellitus.

  3 months

Secondary Outcomes (3)

• Secondary outcome: Changes in Lipid Profile

  3 months

• Secondary Outcome: Safety Monitoring by muscle and metabolic Parameters

  3 months

• Secondary Outcome : Treatment-Related Adverse Effects

  3 months

Study Arms (3)

Rosuvastatin + Ezetimibe

ACTIVE COMPARATOR

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

Drug: Rosuvastatin + Ezetimibe

Bempedoic Acid + Ezetimibe

ACTIVE COMPARATOR

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

Drug: Bempedoic Acid + Ezetimibe

Rosuvastatin + Ezetimibe + Bempedoic Acid

ACTIVE COMPARATOR

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

Drug: Rosuvastatin + Ezetimibe + Bempedoic Acid

Interventions

Rosuvastatin + Ezetimibe DRUG

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

Rosuvastatin + Ezetimibe

Bempedoic Acid + Ezetimibe DRUG

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

Bempedoic Acid + Ezetimibe

Rosuvastatin + Ezetimibe + Bempedoic Acid DRUG

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

Rosuvastatin + Ezetimibe + Bempedoic Acid

Eligibility Criteria

• Age: 35 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Bahria University: lead

Study Sites (1)

National Medical Center

Karachi, Sindh, 75500, Pakistan

Location

Related Publications (8)

• 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.

  PMID: 35346603 BACKGROUND

• 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.

  PMID: 33514449 BACKGROUND

• 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.

  PMID: 31357887 BACKGROUND

• 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.

  PMID: 31714986 BACKGROUND

• 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.

  PMID: 32980290 BACKGROUND

• 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.

  PMID: 34980867 BACKGROUND

• 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.

  PMID: 36876740 BACKGROUND

• 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.

  PMID: 39330344 BACKGROUND

Related Links

• ACC/AHA cholesterol management guidelines
• ADA information on diabetes and cardiovascular risk.

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hypercholesterolemia; Hyperlipoproteinemia Type II; Dyslipidemias

Interventions

Rosuvastatin Calcium; Ezetimibe; 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperlipidemias; Lipid Metabolism Disorders; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azetidines; Azetines

Study Officials

• Fatima Khatoon, MBBS

  Bahria University, Islamabad

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fatima Khatoon, MBBS

CONTACT

+923213334507; fatima.omair@gmail.com

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

CONTACT

+923212794282; syedijaz.bumdc@bahria.edu.pk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2025
• First Posted: December 1, 2025
• Study Start: January 1, 2026
• Primary Completion: March 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: December 1, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: IPD and supporting information will be available after publication of the primary study results and will remain accessible for 3 years following the study completion
• Access Criteria: All data will be accessible to every one

Locations

PA (1)