Retatrutide vs Semaglutide for Type 2 Diabetes

Not currently recruiting at 91 trial locations

Overseen By Neda Rasouli

Age: 18+

Sex: Any

Trial Phase: Phase 3

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 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: 24

Duration: 26 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how well two medications, retatrutide and semaglutide, help people with Type 2 Diabetes manage blood sugar levels when metformin alone isn't sufficient. Researchers aim to assess the effectiveness and safety of these treatments over approximately 26 months. Participants will be divided into groups to receive different doses of retatrutide or semaglutide. Ideal candidates have Type 2 Diabetes, struggle with blood sugar control despite taking metformin, and face challenges like maintaining a stable weight for at least 90 days. As a Phase 3 trial, this is the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking diabetes treatments.

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

Research shows that retatrutide is generally safe for people with type 2 diabetes. Studies have found its safety and tolerability to be similar to other approved diabetes treatments, with most people not experiencing serious side effects. Common side effects were mild, such as nausea, which often occurs with similar drugs.

Semaglutide, already approved by the FDA for treating type 2 diabetes, has been found safe for many people. While some side effects may occur, they are usually mild and manageable.

Overall, both retatrutide and semaglutide are considered safe. Retatrutide has shown similar safety to existing treatments, and semaglutide has proven its safety through FDA approval. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about retatrutide for type 2 diabetes because it offers a potentially new approach compared to existing treatments like metformin, sulfonylureas, and GLP-1 receptor agonists such as semaglutide. Retatrutide is unique because it is a triple agonist, meaning it targets three different receptors involved in glucose and energy balance, which might improve blood sugar control more effectively than current options. Additionally, with its subcutaneous administration, retatrutide could offer a convenient delivery method similar to semaglutide but with enhanced benefits. Overall, this new mechanism of action could lead to better outcomes for patients managing type 2 diabetes.

What evidence suggests that this trial's treatments could be effective for Type 2 Diabetes?

This trial will compare Retatrutide and Semaglutide for managing type 2 diabetes. Research has shown that Retatrutide, which participants in this trial may receive, can significantly reduce body weight and improve energy processing in people with type 2 diabetes. In studies, Retatrutide led to a noticeable decrease in total body fat compared to other treatments. Meanwhile, Semaglutide, another treatment option in this trial, is known for improving blood sugar levels and aiding weight loss. It has helped nearly half of the patients reach their target blood sugar levels and has shown effective weight reduction in many cases. Both treatments are under study for their potential to better manage type 2 diabetes. ^{1 2 3 5 6}

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 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.

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

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Retatrutide
• Semaglutide

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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]

Oral semaglutide, particularly at doses of 14 mg or flexibly dosed, significantly reduced HbA1c levels and body weight in patients with type 2 diabetes compared to other treatments, especially in those with higher baseline HbA1c levels.

The safety profile of oral semaglutide was comparable to that of other treatments, although it was associated with a higher incidence of gastrointestinal adverse events, which were consistent across different patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral semaglutide by subgroups of patient characteristics in the PIONEER phase 3 programme. Aroda, VR., Bauer, R., Christiansen, E., et al.[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]

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, 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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2301972

Triple–Hormone-Receptor Agonist Retatrutide for Obesity In a phase 1b trial involving participants with type 2 diabetes, treatment with retatrutide resulted in a placebo-adjusted least-squares mean weight reduction ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12026077/

Efficacy and safety of retatrutide, a novel GLP-1, GIP, and ... Retatrutide demonstrated significant improvements in body weight and metabolic outcomes among adults with obesity and had an appropriate safety profile.

3. diabetes.org diabetes.org/newsroom/american-diabetes-association-highlights-novel-agent-retatrutide-results-substantial-weight-reduction-people-with-obesity-type-2-diabetes-during-late-breaking-symposium

San Diego, California People taking retatrutide also lost more weight than those who took placebo – the average weight reduction for the 12 mg group was 16.9% (17.2 ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2213858725000920

Effects of retatrutide on body composition in people with ... In adults with type 2 diabetes, retatrutide significantly improved total body fat mass reduction compared with placebo and dulaglutide.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05929079

NCT05929079 | A Study of Retatrutide (LY3437943) in ... The purpose of this study is to is to evaluate the efficacy and safety of retatrutide in participants with type 2 diabetes in participants who have obesity ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S014067362301053X

Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, ... In people with type 2 diabetes, retatrutide showed clinically meaningful improvements in glycaemic control and robust reductions in bodyweight, with a safety ...