Tirzepatide for Type 2 Diabetes

(SURPASS-EARLY Trial)

Not currently recruiting at 119 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests tirzepatide, a drug that might manage type 2 diabetes (T2D) more effectively when started early. Researchers aim to evaluate tirzepatide's efficacy and safety compared to other diabetes treatments. The trial seeks individuals diagnosed with T2D within the past four years who have been managing their condition with metformin and meet specific blood sugar criteria. Participants should not have type 1 diabetes or certain eye, heart, or thyroid conditions. As a Phase 4 trial, tirzepatide is already FDA-approved and proven effective, and this research aims to understand how it benefits more patients.

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 is the safety track record for these treatments?

Research shows that tirzepatide is generally safe for people with type 2 diabetes, helping to lower blood sugar levels and aiding in weight loss. The FDA has approved tirzepatide for treating type 2 diabetes, indicating it has passed strict safety tests for this use.

Earlier studies found that tirzepatide may reduce the risk of serious health problems, such as heart and kidney issues. Like any medication, it can cause side effects, including nausea or digestive problems, but these are usually manageable. Overall, evidence suggests that most people tolerate tirzepatide well. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Tirzepatide is unique because it combines two hormone actions, targeting both GLP-1 and GIP receptors, which are involved in blood sugar regulation. This dual action is different from most standard treatments for type 2 diabetes, such as metformin or insulin, which typically target blood sugar control through single pathways. Researchers are excited about tirzepatide because it not only helps lower blood sugar levels but also supports weight loss, providing a dual benefit that is highly desirable for managing type 2 diabetes.

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

Research has shown that tirzepatide, one of the treatments in this trial, effectively treats type 2 diabetes. Studies have found that it significantly lowers HbA1c levels, crucial for controlling blood sugar. Tirzepatide also aids in reducing body weight, an important factor in diabetes management. It has outperformed some other diabetes medications. Additionally, tirzepatide is associated with fewer heart and kidney problems, common concerns for people with type 2 diabetes. These findings support its use as a strong option for managing this condition. Participants in this trial will receive either tirzepatide or an antihyperglycemic medication as part of intensified conventional care. ^{1 2 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?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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, 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, 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 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, 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, 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, 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 (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]

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]

Citations

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

Clinical Outcomes of Tirzepatide or GLP-1 Receptor ... Treatment with tirzepatide was associated with significantly lower hazards of all-cause mortality and major adverse cardiovascular and kidney events compared ...

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. 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 ...

4. uchicagomedicine.org uchicagomedicine.org/forefront/research-and-discoveries-articles/2024/may/research-on-glp-1-drugs

Research shows GLP-1 drugs are effective but complex Physicians and researchers agree that the drugs are highly effective for weight management and Type 2 diabetes treatment.

5. bmj.com bmj.com/content/384/bmj-2023-076410

Comparative effectiveness of GLP-1 receptor agonists on ... Tirzepatide was the most effective GLP-1RA drug for glycaemic control by reducing haemoglobin A 1c and fasting plasma glucose concentrations.

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK585056/

Tirzepatide - StatPearls - NCBI Bookshelf Tirzepatide is a novel medication approved by the US Food and Drug Administration (FDA) for treating type 2 diabetes mellitus (T2DM).

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 ...