Tirzepatide for Type 2 Diabetes

(SURPASS-EARLY Trial)

Recruiting at 109 trial locations

Overseen By J. Scott Overcash

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Eli Lilly and Company

Must be taking: Metformin

Must not be taking: GLP-1 agonists, Insulin

Disqualifiers: Type 1 diabetes, Pancreatitis, CVD, others

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

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: Unknown

Duration: 104 weeks

780 Participants Needed

Trial Summary

What is the purpose of this trial?

This study aims to investigate the efficacy and safety of tirzepatide in participants with type 2 diabetes (T2D) compared to other existing treatment options when treatment is initiated early.

Will I have to stop taking my current medications?

The trial requires participants to have been on a stable dose of metformin for at least 90 days before starting. If you are taking other diabetes medications, you may need to stop them, but the protocol does not specify this clearly.

What data supports the effectiveness of the drug tirzepatide for type 2 diabetes?

Research shows that tirzepatide significantly lowers blood sugar levels and helps with weight loss in people with type 2 diabetes. In clinical trials, it was more effective than other diabetes medications like semaglutide, with many patients achieving normal blood sugar levels and losing more than 10% of their body weight. ^{1 2 3 4 5}

Is tirzepatide safe for humans?

Tirzepatide has been tested in several clinical trials for type 2 diabetes, showing similar side effects to other medications in its class, like nausea, vomiting, diarrhea, and constipation, especially at higher doses. It has also been found to be safe for the heart, with no increased risk of major cardiovascular events. ^{1 2 4 6 7}

What makes the drug Tirzepatide unique for treating type 2 diabetes?

Tirzepatide is unique because it is a dual-action drug that targets both the GIP and GLP-1 receptors, which helps improve blood sugar control and promotes weight loss. This dual mechanism is different from other treatments that typically target only one of these pathways. ^{4 5 8 9 10}

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

Eligibility Criteria

Adults with type 2 diabetes who have been diagnosed within the last 4 years, currently treated only with metformin, and have HbA1c levels between ≥7% to ≤9.5%. They must not be on insulin or other anti-diabetic meds, have a history of certain thyroid cancers or syndromes (MTC/MEN2), pancreatitis, recent cancer treatments (except skin cancer), weight loss surgery, or severe diabetic eye disease.

Inclusion Criteria

I have been taking only metformin for at least 90 days.

I have been taking metformin consistently for over 90 days.

I was diagnosed with type 2 diabetes in the last 4 years.

Exclusion Criteria

I or a family member have had medullary thyroid cancer or MEN2.

I am taking insulin or other medications for diabetes.

I have been diagnosed with pancreatitis before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tirzepatide or intensified conventional care for type 2 diabetes

104 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants may continue to be monitored for long-term outcomes

104 weeks

Treatment Details

Interventions

• Antihyperglycemic medication
• Tirzepatide

Trial Overview The trial is testing Tirzepatide's effectiveness and safety against standard care in adults with early-stage type 2 diabetes. Participants will either receive Tirzepatide or intensified conventional antihyperglycemic medication to compare outcomes.

Participant Groups

Group I: Tirzepatide Experimental Treatment 1 Intervention

Participants will receive tirzepatide at the maximum tolerated dose subcutaneously (SC)

Group II: Intensified Conventional Care Dose Active Control 1 Intervention

Participants will receive an antihyperglycemic medication

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?

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

Findings from Research

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]

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]

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 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, 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]

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 significantly reduces body weight in patients with type 2 diabetes and obesity, with an average weight loss of -9.81 kg compared to placebo, based on a meta-analysis of 10 studies involving 9,873 patients.

While tirzepatide is effective for weight loss, it has a higher incidence of gastrointestinal side effects compared to placebo, although serious adverse events and hypoglycemia are less common, indicating a need for monitoring these reactions during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight loss efficiency and safety of tirzepatide: A Systematic review. Lin, F., Yu, B., Ling, B., 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]

References

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

Tirzepatide: Clinical review of the "twincretin" injectable. [2023]

2. England 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. [2022]

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

Effects of subcutaneous tirzepatide versus placebo or semaglutide on pancreatic islet function and insulin sensitivity in adults with type 2 diabetes: a multicentre, randomised, double-blind, parallel-arm, phase 1 clinical trial. [2022]

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

Adverse Events Related to Tirzepatide. [2023]

6. Switzerland 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? [2023]

7. England 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. [2022]

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

Weight loss efficiency and safety of tirzepatide: A Systematic review. [2023]

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

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

10. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Tirzepatide: A New Generation Therapeutic for Diabetes Type 2. [2023]