Tirzepatide for Atherosclerosis in Type 2 Diabetes

(T-PLAQUE Trial)

Overseen by Matthew A Budoff, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Matthew J. Budoff

Must be taking: Diabetes medications

Must not be taking: GLP1-RA

Disqualifiers: Type 1 diabetes, Severe hypoglycemia, Pancreatitis, others

Prior Safety Data

Approved in 6 Jurisdictions

Trial Summary

What is the purpose of this trial?

A multi-center, randomized, double-blind, placebo-controlled, parallel-group phase IV Study evaluating the effects of tirzepatide on atherosclerotic plaque progression assessed by coronary computed tomography angiography (CCTA) in participants with a diagnosis of type II Diabetes (T2DM) and atherosclerosis.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but you must be on a stable diabetes medication regimen for more than 4 weeks before starting the trial.

What data supports the effectiveness of the drug Tirzepatide for atherosclerosis in type 2 diabetes?

Tirzepatide, a drug approved for type 2 diabetes, has shown benefits like lowering blood sugar and weight loss, which are important for heart health. Although specific data on atherosclerosis is not available, its positive effects on cardiovascular risk factors suggest it might help with atherosclerosis in type 2 diabetes. ^{1 2 3 4 5}

Is tirzepatide safe for humans?

Tirzepatide has been studied in people with type 2 diabetes and has shown a safety profile similar to other treatments in its class, with no increased risk of major cardiovascular events. It has been approved for use in several countries, indicating it is generally considered safe for humans. ^{1 2 4 6 7}

How is the drug Tirzepatide unique for treating atherosclerosis in type 2 diabetes?

Tirzepatide is unique because it combines the effects of two hormones, GIP and GLP-1, to help control blood sugar and improve heart health. This dual action, known as 'twincretin', not only helps with diabetes management but also shows potential cardiovascular benefits, which could be beneficial for atherosclerosis. ^{2 4 8 9 10}

Research Team

Matthew A Budoff, MD

Principal Investigator

The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Eligibility Criteria

This trial is for adults aged 40-80 with type 2 diabetes and atherosclerosis, who have had the condition for at least 5 years, an HbA1c level of 7.0% to ≤10.5%, and are on stable diabetes medication. They must have two coronary artery plaques visible on CCTA and a BMI ≥25 kg/m². Exclusions include severe heart conditions, recent major cardiovascular events, certain cancers, renal insufficiency, planned surgeries affecting blood vessels or stomach, and allergies to CCTA contrast dye.

Inclusion Criteria

I have been on the same diabetes medication for more than 4 weeks.

Your body mass index (BMI) is 25 or higher.

I use non-oral or additional barrier contraception during my treatment.

Exclusion Criteria

I have been in remission for less than 5 years or have an untreated cancer.

I am planning treatment for eye conditions related to diabetes.

I have had pancreatitis before.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive tirzepatide or placebo for 52 weeks with weekly subcutaneous injections

52 weeks

Weekly visits (in-person or virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Placebo (Drug)
• Tirzepatide (Glucagon-like peptide-1 receptor agonist)

Trial Overview The study tests Tirzepatide's effect on slowing down plaque buildup in arteries compared to a placebo in people with type 2 diabetes using advanced imaging (CCTA). Participants will be randomly assigned to either the drug or placebo group without knowing which one they receive (double-blind design) across multiple centers.

Participant Groups

Group I: Tirzepatide Active Control 1 Intervention

Tirzepatide 15mg Prefilled pen for weekly subcutaneous injection over 52 weeks

Group II: Placebo Placebo Group 1 Intervention

Placebo Prefilled pen (volume matched) for weekly subcutaneous injection over 52 weeks

Tirzepatide is already approved in Canada for the following indications:

Approved in Canada as Mounjaro for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

Matthew J. Budoff

Lead Sponsor

Trials

1

Recruited

120+

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Lead Sponsor

Trials

105

Recruited

46,600+

Joe W. Ramos

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Chief Executive Officer

PhD in Cell Biology from the University of Virginia Medical School

Marianne Gausche-Hill

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Chief Medical Officer since 2023

MD from UCLA

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Findings from Research

In a study involving 2002 adults with type 2 diabetes and high cardiovascular risk, tirzepatide significantly reduced HbA1c levels more than insulin glargine after 52 weeks, with reductions of -2.43% and -2.58% for tirzepatide 10 mg and 15 mg, respectively, compared to -1.44% for glargine.

Tirzepatide was associated with a lower incidence of hypoglycemia (6-9%) compared to glargine (19%), and it did not increase cardiovascular risk, showing it is a safe and effective option for managing diabetes in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Del Prato, S., Kahn, SE., Pavo, I., et al.[2022]

Tirzepatide, a novel GIP/GLP-1 receptor agonist, has shown significant reductions in HbA1c levels and clinically meaningful weight loss in type 2 diabetes patients, with low rates of hypoglycemia, based on results from the SURPASS clinical trial program.

The safety profile of tirzepatide is comparable to existing GLP-1 receptor agonists, and while dedicated cardiovascular and kidney trial results are pending, early indications suggest potential benefits in these areas for individuals with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenging Clinical Perspectives in Type 2 Diabetes with Tirzepatide, a First-in-Class Twincretin. MacIsaac, RJ., Deed, G., D'Emden, M., et al.[2023]

Tirzepatide, a dual agonist for GIPR and GLP-1R, has been shown to significantly improve glycemic control in patients with type 2 diabetes mellitus (T2DM) compared to baseline, placebo, and other active treatments.

The medication is associated with weight loss and improvements in certain cardiovascular and liver health markers, while maintaining a favorable safety profile with a low risk of hypoglycemia, although gastrointestinal side effects were common and could lead to discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile of tirzepatide in the management of type 2 diabetes mellitus: design, development, and place in therapy. Naseralallah, L., Aboujabal, B.[2023]

Tirzepatide demonstrated a dose-dependent ability to lower HbA1c levels in adults with type 2 diabetes, with reductions ranging from -17.71 to -22.35 mmol/mol compared to placebo, and was also more effective in reducing body weight than other treatments.

While tirzepatide did not increase the risk of hypoglycaemia compared to placebo and showed lower rates than basal insulin, it was associated with a higher incidence of gastrointestinal side effects, particularly nausea and vomiting, especially at the 15 mg dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: a systematic review and meta-analysis. Karagiannis, T., Avgerinos, I., Liakos, A., et al.[2023]

Tirzepatide, a novel incretin coagonist approved for type 2 diabetes, targets both GLP-1 and GIP receptors, potentially addressing defects in the incretin hormone system that contribute to diabetes.

Phase 2 and 3 trials indicate that tirzepatide effectively lowers hemoglobin A1c and promotes weight loss, with a safety profile showing mostly mild gastrointestinal side effects and a low risk of treatment discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Dual Incretin Agent, Tirzepatide (LY3298176), for the Treatment of Type 2 Diabetes Mellitus and Cardiometabolic Health. Bucheit, J., Ayers, J., Pamulapati, L., et al.[2022]

In a meta-analysis of seven randomized controlled trials involving 4,887 participants treated with tirzepatide, the drug did not increase the risk of major adverse cardiovascular events (MACE-4) compared to control groups, indicating a favorable safety profile for cardiovascular outcomes.

The hazard ratios for MACE-4 and cardiovascular death were 0.80 and 0.90 respectively, suggesting that tirzepatide may even be associated with a reduced risk of these events, particularly in participants with high cardiovascular risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis. Sattar, N., McGuire, DK., Pavo, I., et al.[2022]

Tirzepatide is a new diabetes treatment that effectively controls blood glucose levels by activating both GIP and GLP-1 receptors, which help stimulate insulin secretion and have additional metabolic benefits.

In clinical trials, Tirzepatide not only improved glycemic control but also showed positive effects on blood pressure and lipid levels, leading to its FDA approval for use as a standalone or combination therapy in diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide: A Systematic Update. Forzano, I., Varzideh, F., Avvisato, R., et al.[2022]

Tirzepatide, a dual GLP-1 and GIP receptor agonist, has shown significant reductions in glycated hemoglobin levels and body weight in patients with type 2 diabetes mellitus (T2DM) during phase 3 clinical trials.

In addition to its glucose-lowering and weight loss effects, tirzepatide may also offer cardiovascular benefits, highlighting its potential as a comprehensive treatment for T2DM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Cardiovascular Effect of Tirzepatide: A Glucagon-Like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide Dual Agonist. Cho, YK., La Lee, Y., Jung, CH.[2023]

Tirzepatide is a dual GIP/GLP-1 receptor agonist that can be administered once a week, showing significant improvements in glycemic control, insulin sensitivity, and body weight in patients with type 2 diabetes mellitus (T2DM) based on phase 1, 2, and 3 clinical trials.

The drug not only helps lower blood sugar levels but also positively affects lipid metabolism, making it a promising treatment option for T2DM and related cardiometabolic disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide - a dual GIP/GLP-1 receptor agonist - a new antidiabetic drug with potential metabolic activity in the treatment of type 2 diabetes. Nowak, M., Nowak, W., Grzeszczak, W.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Challenging Clinical Perspectives in Type 2 Diabetes with Tirzepatide, a First-in-Class Twincretin. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Profile of tirzepatide in the management of type 2 diabetes mellitus: design, development, and place in therapy. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: a systematic review and meta-analysis. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

A Novel Dual Incretin Agent, Tirzepatide (LY3298176), for the Treatment of Type 2 Diabetes Mellitus and Cardiometabolic Health. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Comparison of tirzepatide and dulaglutide on major adverse cardiovascular events in participants with type 2 diabetes and atherosclerotic cardiovascular disease: SURPASS-CVOT design and baseline characteristics. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Tirzepatide: A Systematic Update. [2022]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

The Cardiovascular Effect of Tirzepatide: A Glucagon-Like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide Dual Agonist. [2023]

10. Poland pubmed.ncbi.nlm.nih.gov

Tirzepatide - a dual GIP/GLP-1 receptor agonist - a new antidiabetic drug with potential metabolic activity in the treatment of type 2 diabetes. [2022]