Tirzepatide vs Dulaglutide for Type 2 Diabetes

(SURPASS-CVOT Trial)

No longer recruiting at 1330 trial locations

Overseen By Anjanette Tan

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

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

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 54 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares the effectiveness and safety of two treatments, tirzepatide (a GIP/GLP-1 receptor agonist) and dulaglutide (a GLP-1 receptor agonist), for individuals with type 2 diabetes who face a higher risk of heart problems. Participants will receive one of the treatments weekly to determine which better controls blood sugar and improves heart health. Those diagnosed with type 2 diabetes and heart disease, such as a history of heart attack or stroke, might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, providing an opportunity to contribute to groundbreaking advancements in diabetes treatment.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that tirzepatide effectively lowers blood sugar and aids weight loss in people with type 2 diabetes. Although approved for managing diabetes and weight, real-world safety data remains limited. Some participants have experienced side effects, but detailed numbers are not always available.

Dulaglutide is another treatment for type 2 diabetes. Research has found it to be safe, with the most common side effects being stomach issues and reactions at the injection site, affecting about 11.80% and 8.89% of participants, respectively. Overall, dulaglutide has manageable side effects.

Both treatments are taken weekly. While they offer benefits, discussing potential risks and side effects with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about tirzepatide for type 2 diabetes because it offers a novel approach by acting on both the GLP-1 and GIP receptors, setting it apart from standard treatments that typically target just the GLP-1 receptor, like dulaglutide. This dual action may enhance glucose control and weight loss more effectively than current options. Additionally, tirzepatide is administered once a week via a subcutaneous injection, similar to dulaglutide, making it a convenient option for patients.

What evidence suggests that this trial's treatments could be effective for type 2 diabetes?

This trial will compare tirzepatide and dulaglutide for managing type 2 diabetes. Studies have shown that tirzepatide, one of the treatments in this trial, significantly lowers A1C levels and aids in weight loss more effectively than some other treatments. Research indicates that tirzepatide also reduces the risk of major heart and kidney problems. Dulaglutide, the other treatment option, helps control blood sugar by lowering A1C levels and is effective for both adults and youths with type 2 diabetes. Both treatments are injected once a week and show promise in managing diabetes and related health risks. ^{1 3 4 6 7}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

This trial is for adults with type 2 diabetes who are overweight (BMI ≥25 kg/m²) and have a history of heart disease. They should have an HbA1c level between 7.0% to ≤10.5%. People with plans for certain eye treatments, gastric surgeries, or those with type 1 diabetes, recent severe blood loss, pancreatitis, or major cardiovascular events in the last two months cannot join.

Inclusion Criteria

I have been diagnosed with type 2 diabetes.

I have been diagnosed with heart disease caused by hardened arteries.

You are considered overweight based on your height and weight.

Exclusion Criteria

I have a known issue with my stomach emptying or have had/planning stomach surgery.

I or my family have a history of MTC or MEN-2.

I have not had a blood transfusion or severe blood loss in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either tirzepatide or dulaglutide administered subcutaneously once a week

54 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dulaglutide
• Tirzepatide

Trial Overview The study compares Tirzepatide (LY3298176) to Dulaglutide in reducing heart-related issues in people with type 2 diabetes at increased risk of cardiovascular events. It aims to see which drug is more effective and safe.

How Is the Trial Designed?

Group I: Tirzepatide Experimental Treatment 1 Intervention

Tirzepatide administered subcutaneously (SC) once a week.

Group II: Dulaglutide Active Control 1 Intervention

Dulaglutide administered SC once a week.

Dulaglutide is already approved in United States, European Union for the following indications:

Approved in United States as Trulicity for:

• Type 2 diabetes mellitus
• Cardiovascular risk reduction in adults with established cardiovascular disease or multiple cardiovascular risk factors

Approved in European Union as Trulicity for:

• Type 2 diabetes mellitus
• Cardiovascular risk reduction in adults with established cardiovascular disease or multiple cardiovascular risk factors

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead 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

Tirzepatide, a dual GIP and GLP-1 receptor agonist, has a safety profile similar to other GLP-1 receptor agonists, but higher doses (10mg and above) are associated with increased risks of hypoglycemia and treatment discontinuation.

In clinical trials involving 9818 patients, higher doses of tirzepatide led to more frequent gastrointestinal side effects like nausea, vomiting, and diarrhea, indicating that these adverse events are dose-dependent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of the safety of tirzepatide-a new dual GLP1 and GIP agonist - is its safety profile acceptable? Meng, Z., Yang, M., Wen, H., et al.[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 (Mounjaro™) is a new treatment for type 2 diabetes that acts on both GIP and GLP-1 receptors, showing strong results in lowering blood glucose and promoting weight loss based on evidence from five SURPASS clinical trials.

The safety profile of tirzepatide is similar to that of existing GLP-1 receptor agonists, making it a promising option for early intervention in managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug: Tirzepatide (Mounjaro™). Gettman, L.[2023]

Tirzepatide, a new medication approved by the FDA, acts as an agonist for both GLP-1 and GIP receptors, which helps improve blood sugar control in patients with type II diabetes when combined with diet and exercise.

This drug represents a significant advancement in diabetes management, offering a new approach to treatment by targeting multiple pathways involved in glucose regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide: A New Generation Therapeutic for Diabetes Type 2. Al-Horani, RA., Chedid, M.[2023]

Tirzepatide, approved in 2022, is a novel treatment for type 2 diabetes that acts on both GLP-1 and GIP pathways, showing significant efficacy in lowering blood sugar levels and promoting weight loss in various patient groups.

Clinical trials, including the SURPASS and SURMOUNT studies, indicate that tirzepatide has a safety profile similar to traditional GLP-1 receptor agonists, with common gastrointestinal side effects, making it a promising option for patients needing better glycemic and weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide: Clinical review of the "twincretin" injectable. Krauss, Z., Hintz, A., Fisk, R.[2023]

In a phase 3 trial involving 636 Japanese adults with type 2 diabetes, tirzepatide demonstrated superior efficacy in lowering HbA1c levels compared to dulaglutide, with reductions of -2.4% to -2.8% for tirzepatide versus -1.3% for dulaglutide after 52 weeks.

Tirzepatide also led to significant weight loss, with reductions ranging from -5.8 kg to -10.7 kg depending on the dose, while dulaglutide resulted in only a -0.5 kg reduction, indicating its potential as an effective treatment for both glycemic control and weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tirzepatide monotherapy compared with dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono): a double-blind, multicentre, randomised, phase 3 trial. Inagaki, N., Takeuchi, M., Oura, T., et al.[2022]

Tirzepatide, a novel GLP-1 receptor agonist, has been shown to significantly reduce A1C levels and body weight in patients with type 2 diabetes compared to placebo and other active treatments.

The safety profile of tirzepatide is similar to other GLP-1 receptor agonists, with the most common side effects being mild to moderate gastrointestinal issues, and it does not increase the risk of hypoglycemia, making it a promising treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Tirzepatide in Adults With Type 2 Diabetes: A Perspective for Primary Care Providers. Kushner, P., Anderson, JE., Simon, J., et al.[2023]

Tirzepatide, a medication for type 2 diabetes, shows a dose-dependent increase in gastrointestinal adverse events (AEs), with nausea and diarrhea being the most common, affecting up to 49% of participants at the highest dose (15 mg).

Despite the gastrointestinal side effects, serious adverse events like severe hypoglycemia and acute pancreatitis are rare (≤ 1%), indicating that tirzepatide is generally safe for use in patients with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events Related to Tirzepatide. Mishra, R., Raj, R., Elshimy, G., et al.[2023]

Tirzepatide, the first dual GIP/GLP-1 receptor co-agonist approved for type 2 diabetes, significantly reduces HbA1c levels (by 1.24 to 2.58%) and body weight (by 5.4-11.7 kg) in clinical trials involving type 2 diabetic patients, outperforming the selective GLP-1 RA semaglutide.

The safety profile of tirzepatide is similar to that of other GLP-1 receptor agonists, with common side effects including nausea and diarrhea, and it shows potential cardiovascular safety, as no significant increase in major adverse cardiovascular events was observed during the trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regrading glycaemic control and body weight reduction. Nauck, MA., D'Alessio, DA.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7324465/

Real-World Effectiveness of Dulaglutide in Patients with ... Studies consistently demonstrated that dulaglutide improved glycemic control by reducing HbA1c levels from pre-treatment. Furthermore, treatment ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7896253/

Efficacy and Safety of Dulaglutide 3.0 mg and 4.5 mg Versus ... To compare efficacy and safety of dulaglutide at doses of 3.0 and 4.5 mg versus 1.5 mg in patients with type 2 diabetes inadequately controlled with metformin.

3. trulicity.lilly.com trulicity.lilly.com/hcp/efficacy-weight

Clinical Trials: Lowereing A1C, Weight Change & CV Data In the AWARD-11 study, adults with type 2 diabetes taking Trulicity had a reduction in their A1C from the mean baseline of 8.6% at 36 weeks.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2589936824000161

Comparative efficacy and safety of weekly dulaglutide ... Dulaglutide, particularly at higher doses, demonstrates superior efficacy in lowering hemoglobin A1C and reducing hypoglycemia risk compared to Icodec insulin.

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2204601

Once-Weekly Dulaglutide for the Treatment of Youths with ... Results from this double-blind, randomized, phase 3 trial showed that dulaglutide treatment was superior to placebo in reducing the glycated hemoglobin level ...

6. e-dmj.org e-dmj.org/journal/view.php?number=2809

Safety and Effectiveness of Dulaglutide in the Treatment ... The most common AEs associated with dulaglutide were gastrointestinal disorders (11.80%) plus general disorders and administration site conditions (8.89%).

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12469573/

Real-World Safety Concerns of Tirzepatide ... receptor agonist, is approved for type 2 diabetes and weight management. Despite its efficacy, real-world safety data remain limited. This ...