Tirzepatide for Atherosclerosis in Type 2 Diabetes

(T-PLAQUE Trial)

Overseen By Ferdinand Flores, BS

Age: 18+

Sex: Any

Trial Phase: Phase 4

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 This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 52 weeks

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if tirzepatide can slow or halt plaque growth in the arteries of individuals with type 2 diabetes and atherosclerosis. Tirzepatide, administered as a weekly injection, will be compared to a placebo (a treatment with no active drug). The study seeks participants who have had type 2 diabetes for at least 5 years, have specific artery plaque, and are currently managing their diabetes with medication. As a Phase 4 trial, this research helps to understand how the already FDA-approved and effective treatment benefits a broader range of patients.

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 is the safety track record for tirzepatide?

Research shows that tirzepatide is generally well-tolerated. Studies have demonstrated its effectiveness in managing type 2 diabetes and obesity. The FDA has approved it for treating type 2 diabetes, confirming its safety for that condition.

One study linked tirzepatide to lower risks of death and major heart and kidney problems, indicating its effectiveness and safety for people with type 2 diabetes. Another study found that tirzepatide reduced blood sugar levels and body weight more than some other diabetes treatments. While these results are promising, some participants experienced side effects like nausea or digestive issues.

Overall, tirzepatide is considered safe, especially as an FDA-approved treatment for diabetes. Prospective participants should consult a healthcare provider about any concerns before joining a clinical trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Tirzepatide is unique because it targets both the GLP-1 and GIP receptors, unlike many current treatments for atherosclerosis in Type 2 diabetes, which typically focus on just one. This dual-action approach could potentially offer better control of blood sugar and weight, both of which are crucial for managing atherosclerosis. Researchers are particularly excited about its weekly subcutaneous injection method, which may increase convenience and adherence compared to daily medications.

What is the effectiveness track record for tirzepatide in treating atherosclerosis in type 2 diabetes?

Studies have shown that tirzepatide, which participants in this trial may receive, can help people with type 2 diabetes by lowering blood sugar levels and reducing body weight. Research also suggests it might improve heart health by lowering the risk of major heart problems, such as heart attacks. An observational study found that people with type 2 diabetes who used tirzepatide had better heart health. Tirzepatide targets two hormones that influence insulin and appetite. This combination has proven effective in managing diabetes and could aid artery health by affecting plaque buildup. ^{1 3 4 6 7}

Who Is on the Research Team?

Matthew A Budoff, MD

Principal Investigator

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

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Tirzepatide

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.

How Is the Trial Designed?

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 United States, European Union, Canada, United Kingdom for the following indications:

Approved in United States as Mounjaro for:

• Type 2 diabetes

Approved in European Union as Mounjaro for:

• Type 2 diabetes

Approved in Canada as Mounjaro for:

• Type 2 diabetes

Approved in United States as Zepbound for:

• Weight loss
• Moderate to severe obstructive sleep apnea

Approved in United Kingdom as Zepbound for:

• Weight loss

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+

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

Published Research Related to This Trial

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, a once-weekly GIP/GLP-1 receptor agonist, is being evaluated in a large cardiovascular outcomes trial involving 13,299 participants with type 2 diabetes and established cardiovascular disease to assess its safety and efficacy compared to dulaglutide.

The primary goal of the trial is to determine if tirzepatide is noninferior to dulaglutide in preventing major adverse cardiovascular events (MACE), which will help establish its cardiovascular benefits in this patient population.

NCBI (Pubmed)

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. Nicholls, SJ., Bhatt, DL., Buse, JB., et al.[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]

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, 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]

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]

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 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 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 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]

Citations

1. investor.lilly.com investor.lilly.com/news-releases/news-release-details/lillys-mounjaro-tirzepatide-gipglp-1-dual-agonist-demonstrated

Lilly's Mounjaro (tirzepatide), a GIP/GLP-1 dual agonist ... [Trulicity is also used in adults with type 2 diabetes to reduce the risk of major cardiovascular events (problems having to do with the heart ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40214900/

Efficacy and Safety of Tirzepatide Compared with GLP-1 ... Tirzepatide demonstrated statistically significantly greater reductions in HbA1c and body weight when compared with selected GLP-1 RAs and ...

3. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2822209

Clinical Outcomes of Tirzepatide or GLP-1 Receptor ... This cohort study investigates the risks of mortality and adverse cardiovascular and kidney outcomes among individuals with type 2 diabetes ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2206038

Tirzepatide Once Weekly for the Treatment of Obesity Tirzepatide is a once-weekly subcutaneous injectable peptide (approved by the Food and Drug Administration [FDA] for type 2 diabetes) engineered ...

5. jacc.org jacc.org/doi/10.1016/j.jacadv.2025.101740

An Observational Study of Cardiovascular Outcomes ... Tirzepatide use is associated with better outcomes in adults aged 40 years or older with T2DM, body mass index ≥25 kg/m 2 , and pre-existing IHD.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30473097/

LY3298176, a novel dual GIP and GLP-1 receptor agonist ... The data warrant further clinical evaluation of LY3298176 for the treatment of T2DM and potentially obesity. Keywords: Glucagon-like peptide-1; Glucose- ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04657003

NCT04657003 | A Study of Tirzepatide (LY3298176) in ... This is a study of tirzepatide in participants with type 2 diabetes who have obesity or are overweight. The main purpose is to learn more about how tirzepatide ...