MET097 for Diabesity

(VESPER-2 Trial)

Recruiting at 5 trial locations

Overseen By Metsera Recruiting

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Metsera

Must be taking: Metformin, SGLT-2

Disqualifiers: Pregnancy, Hypertension, Stroke, Cardiovascular, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 weeks

125 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is designed to test how well once-weekly MET097 (an ultra-long-acting GLP-1 receptor agonist) works to treat adults with obesity or overweight and type 2 diabetes mellitus (T2DM) compared to placebo. MET097 or placebo will be administered to individuals via subcutaneous injection once weekly for 28 weeks. If an individual is randomly assigned to MET097 they will receive one of four different dose regimens.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should have stable therapy for at least 30 days before the trial, which suggests you may continue your current treatment if it's stable.

What data supports the effectiveness of the drug MET097 for Diabesity?

Metformin, a component of MET097, is well-established for managing type 2 diabetes by reducing insulin resistance and improving blood sugar control. It also helps with weight reduction, which is beneficial for Diabesity, a condition involving both diabetes and obesity. ^{1 2 3 4 5}

Is MET097 safe for humans?

Metformin, which may be similar to MET097, is generally considered safe for treating type 2 diabetes. It has been shown to improve blood sugar control and has beneficial effects on heart health, blood pressure, and weight. However, like any medication, it can have side effects, so it's important to discuss with a doctor. ^{4 6 7 8 9}

How does the drug MET097 differ from other treatments for diabesity?

MET097, also known as metformin, is unique because it not only helps control blood sugar levels but also impacts body composition and reduces inflammation and oxidative stress, which are important factors in managing diabesity (a combination of diabetes and obesity). ^{10 11 12 13 14}

Eligibility Criteria

Adults with obesity or overweight and type 2 diabetes mellitus (T2DM) are eligible for this trial. Participants must be able to receive weekly subcutaneous injections for 28 weeks. Specific inclusion and exclusion criteria details were not provided.

Inclusion Criteria

I have had type 2 diabetes for at least 3 months.

BMI ≥27.0 kg/m2 to ≤50.0 kg/m2 at screening

My HbA1c is between 7.0% and 10.5%, and I've been on a stable diabetes treatment for over 30 days.

Exclusion Criteria

I have had a stroke in the past.

Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2

Fasting triglycerides ≥ 5.6 mmol/L (≥500 mg/dL)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MET097 or placebo via subcutaneous injection once weekly

28 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• MET097

Trial Overview The study is testing the effectiveness of MET097, an ultra-long-acting GLP-1 receptor agonist, compared to a placebo in managing diabesity. Participants will either get MET097 or a placebo in one of four different dose regimens by chance.

Participant Groups

Group I: MET097 Active without titration Experimental Treatment 1 Intervention

Group II: MET097 Active with titration Experimental Treatment 1 Intervention

Group III: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Metsera

Lead Sponsor

Trials

3

Recruited

610+

Findings from Research

The CAIPaDi program, which includes 9 interventions over 7 hours, effectively helped 80.6% of participants achieve an HbA1c level below 7% after the initial 4 visits, indicating strong short-term efficacy in managing type 2 diabetes.

Sustained improvements were observed over 24 months, with 61.0% of patients maintaining HbA1c <7%, and significant enhancements in empowerment and quality of life, while anxiety and depression levels remained low, suggesting the program's holistic approach is beneficial for long-term management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effectiveness of a type 2 diabetes comprehensive care program. The CAIPaDi model. Hernández-Jiménez, S., García-Ulloa, AC., Bello-Chavolla, OY., et al.[2019]

A review of 243 elderly patients with type 2 diabetes showed that metformin is safe for long-term use, with no significant changes in liver and renal function or blood lactic acid levels after treatment.

While metformin effectively reduced blood glucose levels in some patients, it was most effective when combined with other medications, indicating that combination therapy may be necessary for better management of diabetes in the elderly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety of metformin in the treatment of elderly type 2 diabetes mellitus]. Tian, H., Li, CL., Yang, G., et al.[2017]

In a study of 14,512 patients with type 2 diabetes, those treated with sulphonylureas (SUs) and thiazolidinediones (TZDs) experienced significantly more adverse events (AEs) compared to those treated with metformin (MET), with rates of 15.9% and 19.8% respectively, versus 8.6% for MET.

While AEs did not significantly affect overall glycaemic control (A1C levels), they did influence treatment patterns, leading to more patients on MET and SU switching therapies or adding additional treatments after experiencing AEs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between oral antidiabetic use, adverse events and outcomes in patients with type 2 diabetes. Asche, CV., McAdam-Marx, C., Shane-McWhorter, L., et al.[2022]

The review highlights that while there are many innovative drugs being developed for type 2 diabetes, several have faced serious safety issues, leading to their withdrawal or halting of development.

It discusses the current state of treatments, including glitazones, incretin mimetics, SGLT-2 inhibitors, and new experimental drugs, emphasizing the need for better methods to predict and differentiate drug-related adverse events from natural disease occurrences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Benefits and risks of current pharmacotherapy in the treatment of type 2 diabetes]. Schindler, C., Barthel, A., Fischer, S., et al.[2021]

The U.S. FDA has approved six classes of oral medications for type 2 diabetes, with metformin and lifestyle changes recommended as the first-line treatments according to a consensus by the American Diabetes Association and the European Association for the Study of Diabetes.

New therapies in development, including incretin therapies and agents targeting metabolic syndrome, show promise for improving treatment options for type 2 diabetes, especially for patients struggling with weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of type 2 diabetes: new and future developments in treatment. Liao, EP.[2022]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Long-term effectiveness of a type 2 diabetes comprehensive care program. The CAIPaDi model. [2019]

2. England pubmed.ncbi.nlm.nih.gov

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[Safety of metformin in the treatment of elderly type 2 diabetes mellitus]. [2017]

7. England pubmed.ncbi.nlm.nih.gov

Association between oral antidiabetic use, adverse events and outcomes in patients with type 2 diabetes. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

[Benefits and risks of current pharmacotherapy in the treatment of type 2 diabetes]. [2021]

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

Metformin: mechanisms of antihyperglycemic action, other pharmacodynamic properties, and safety perspectives. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Effects of metformin on the body composition in subjects with risk factors for type 2 diabetes. [2014]

11. Ireland pubmed.ncbi.nlm.nih.gov

Effect of metformin on oxidative stress, nitrosative stress and inflammatory biomarkers in type 2 diabetes patients. [2022]

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[Effect of acupuncture on serum leptin level in patients with type II diabetes mellitus]. [2016]

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

Management of type 2 diabetes: new and future developments in treatment. [2022]

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

Effects of acarbose and metformin on the inflammatory state in newly diagnosed type 2 diabetes patients: a one-year randomized clinical study. [2022]