Retatrutide vs Semaglutide for Type 2 Diabetes

Recruiting in Palo Alto (17 mi)

+86 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Eli Lilly and Company

Must be taking: Metformin, SGLT2i

Must not be taking: Weight loss drugs

Disqualifiers: Type 1 diabetes, Severe hypoglycemia, Obesity surgery, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The purpose of this study is to investigate the efficacy and safety of retatrutide compared with semaglutide in participants with Type 2 Diabetes and inadequate glycemic control with metformin with or without sodium-glucose cotransporter-2 inhibitor (SGLT2i). The study will last about 26 months and may include up to 24 visits.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must have been on a stable diabetes treatment with metformin, with or without SGLT2 inhibitors, for at least 90 days before joining. If you're taking weight loss medications, you must stop them 90 days before the trial.

Is semaglutide safe for humans?

Semaglutide, used in treatments like Rybelsus and Ozempic, has been shown to be safe in large clinical trials for people with type 2 diabetes, with a tolerability profile similar to other drugs in its class. It is generally well-tolerated and has been linked to reduced cardiovascular events and weight loss, with a lower risk of low blood sugar. ^{1 2 3 4 5}

How does the drug Retatrutide differ from other treatments for type 2 diabetes?

Retatrutide is being compared to semaglutide, which is unique because it can be taken orally (as Rybelsus) or as a once-weekly injection (as Ozempic), offering flexibility in administration. Semaglutide is a GLP-1 receptor agonist that not only lowers blood sugar but also aids in weight loss and may have cardiovascular and kidney benefits. ^{1 2 3 6 7}

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

This trial is for adults with Type 2 Diabetes who aren't managing their blood sugar well using metformin alone or with an SGLT2 inhibitor. Participants should be committed to the study duration of about 26 months and up to 24 visits.

Inclusion Criteria

I have Type 2 Diabetes.

I have been taking at least 1500 mg of metformin daily for diabetes, with or without SGLT2i, for the last 90 days.

Are of stable weight for at least 90 days prior to screening

Exclusion Criteria

Have Type 1 Diabetes (T1D)

I have had or am planning to have surgery for weight loss.

Have a known clinically significant gastric emptying abnormality

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either retatrutide or semaglutide administered subcutaneously

26 months

Up to 24 visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Retatrutide (GLP-1 Receptor Agonist)
• Semaglutide (GLP-1 Receptor Agonist)

Trial Overview The trial is testing the effectiveness and safety of a new diabetes medication, Retatrutide, compared to an existing one, Semaglutide. It aims to see which better controls blood sugar levels in participants over the course of the study.

Participant Groups

Group I: Retatrutide Dose Level 2 Experimental Treatment 1 Intervention

Participants will receive retatrutide administered SC.

Group II: Retatrutide Dose Level 1 Experimental Treatment 1 Intervention

Participants will receive retatrutide administered subcutaneously (SC).

Group III: Semaglutide Active Control 1 Intervention

Participants will receive semaglutide administered SC.

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

Oral semaglutide (Rybelsus®) has been shown to provide better glycaemic control and promote weight loss in patients with type 2 diabetes (T2DM) compared to standard oral glucose-lowering medications, based on data from the PIONEER clinical trial program involving 9543 patients.

The safety profile of oral semaglutide is similar to other GLP-1 receptor agonists, and it demonstrated cardiovascular safety comparable to placebo in high-risk patients, making it a viable option for T2DM management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus®)]. Paquot, N.[2022]

Semaglutide (Ozempic®) is an effective once-weekly treatment for type 2 diabetes, showing superior glucose-lowering effects and greater weight loss compared to other GLP-1 receptor agonists in Phase III clinical trials.

It is approved for use in Belgium for patients with type 2 diabetes who have not achieved adequate control with other antidiabetic therapies, particularly in those with a body mass index of 30 kg/m² or higher.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Semaglutide, once weekly GLP-1 receptor agonist (Ozempic®)]. Scheen, AJ.[2019]

Oral semaglutide (Rybelsus®), a GLP-1 receptor agonist, not only helps lower blood sugar levels in people with type 2 diabetes but also promotes significant weight loss and has a lower risk of causing hypoglycemia.

Clinical studies indicate that GLP-1 receptor agonists are safe for individuals with type 2 diabetes and chronic kidney disease, and they may offer additional benefits such as protecting kidney function and reducing the risk of major cardiovascular events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Peptide in a Pill - Oral Semaglutide in the Management of Type 2 Diabetes. Selvarajan, R., Subramanian, R.[2023]

Semaglutide, marketed as Rybelsus, is the first oral glucagon-like peptide receptor agonist approved by the FDA in 2019 for treating type 2 diabetes, highlighting its innovative delivery method.

This medication, taken once daily, aids in glucose control and weight management, potentially leading to improved health outcomes for individuals with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide Is a New Once-Daily Oral Medication to Treat Type 2 Diabetes. Blakely, KK., Weaver, K.[2021]

Semaglutide, a GLP-1 receptor agonist with a long half-life, effectively promotes insulin secretion in a glucose-dependent manner, making it a valuable treatment for type 2 diabetes, approved for use worldwide and in Japan since 2018.

Oral semaglutide (Rybelsus®) is the first GLP-1 receptor agonist available in pill form, showing continuous benefits in glycemic control for patients with type 2 diabetes across various stages, as demonstrated in multiple global clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New drug for type 2 diabetes: introduction of oral Semaglutide (Rybelsus® tablets), an oral GLP-1 receptor agonist]. Miyasaka, K.[2022]

Semaglutide (Ozempic®) is a new subcutaneous treatment for type 2 diabetes that effectively lowers blood glucose levels by stimulating insulin release and also helps reduce body weight.

The once-weekly injection has been approved in the US, Puerto Rico, and Canada, and is also under review in other countries, with ongoing clinical development for additional conditions like obesity and liver diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide: First Global Approval. Dhillon, S.[2019]

References

1. Belgium pubmed.ncbi.nlm.nih.gov

[Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus®)]. [2022]

2. Belgium pubmed.ncbi.nlm.nih.gov

[Semaglutide, once weekly GLP-1 receptor agonist (Ozempic®)]. [2019]

3. New Zealand pubmed.ncbi.nlm.nih.gov

A Peptide in a Pill - Oral Semaglutide in the Management of Type 2 Diabetes. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral semaglutide by subgroups of patient characteristics in the PIONEER phase 3 programme. [2022]

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

Semaglutide Is a New Once-Daily Oral Medication to Treat Type 2 Diabetes. [2021]

6. Japan pubmed.ncbi.nlm.nih.gov

[New drug for type 2 diabetes: introduction of oral Semaglutide (Rybelsus® tablets), an oral GLP-1 receptor agonist]. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Semaglutide: First Global Approval. [2019]