Metreleptin for Insulin Resistance

Overseen By Rebecca J Brown, M.D.

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Must not be taking: Anorexigenic drugs

Disqualifiers: Pregnancy, Infectious liver disease, HIV, Alcohol abuse, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called metreleptin for people with diabetes that doesn't respond well to regular treatments. It targets individuals with specific genetic mutations that complicate blood sugar control. The goal is to determine if metreleptin can better manage blood sugar over one year. Suitable participants have severe insulin resistance due to a genetic defect and struggle with high blood sugar levels. The study occurs at the NIH Clinical Center. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team.

Is there any evidence suggesting that metreleptin is likely to be safe for humans?

Previous studies have generally shown that metreleptin is well-tolerated by patients. Common side effects, such as headaches, low blood sugar, weight loss, and stomach pain, affected 10% or more of participants. Although these side effects are not serious, important safety warnings must be considered. There is a risk of developing a serious type of cancer called lymphoma. The FDA has already approved metreleptin for other conditions, like generalized lipodystrophy, indicating prior safety testing. However, weighing the risks carefully is crucial. Participants should always discuss potential risks and benefits with a healthcare provider before joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for insulin resistance, which often involve lifestyle changes and medications like metformin, metreleptin targets the body's leptin pathways. Metreleptin is a synthetic form of leptin, a hormone that helps regulate energy balance and glucose metabolism. By directly addressing leptin deficiencies, this treatment could offer a new mechanism of action that current therapies don't target. Researchers are excited about metreleptin because it opens up the possibility of managing insulin resistance in a fundamentally different way, potentially improving outcomes for patients who don't respond well to existing options.

What evidence suggests that metreleptin might be an effective treatment for insulin resistance?

Research has shown that metreleptin, the treatment under study in this trial, can help control blood sugar in people with certain genetic conditions. Studies have found that metreleptin lowers hemoglobin A1c, an important measure of long-term blood sugar levels. It also improves insulin sensitivity, helping the body use insulin more effectively. Additionally, metreleptin has been linked to better blood fat levels and liver health. These findings suggest that metreleptin could be a promising option for managing diabetes in patients with insulin receptor mutations. ^{2 6 7 8 9}

Who Is on the Research Team?

Rebecca J Brown, M.D.

Principal Investigator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Are You a Good Fit for This Trial?

This trial is for males and females over the age of 5 with severe insulin resistance due to insulin receptor mutations. Participants must have diabetes as defined by ADA criteria, with fasting insulin >30 micro U/ml or glucose levels indicating diabetes. Pregnant women, those not using birth control, or with certain infections like HIV are excluded.

Inclusion Criteria

Fasting insulin >30 micro U/ml

I have diabetes symptoms and my blood sugar level is 200 mg/dL or higher.

I have severe insulin resistance due to issues with my insulin receptor.

Exclusion Criteria

I have a liver infection.

Subjects who have a known hypersensitivity to E. Coli derived proteins

I am HIV positive.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Open label study of metreleptin, 0.2 mg/kg/day (max dose 0.24 mg/kg/day) administered via subcutaneous injections

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Metreleptin

Trial Overview The study tests if metreleptin therapy (0.2 mg/kg/day) can improve blood sugar control in patients with genetic defects in the insulin receptor over a year. It's an open-label study at NIH Clinical Center focusing on changes in Hemoglobin A1c and other blood sugar markers.

How Is the Trial Designed?

Group I: Leptin Treatment Experimental Treatment 1 Intervention

300 mg of study drug administered via subcutaneous (SC) injections.

Metreleptin is already approved in United States, Canada for the following indications:

Approved in United States as Myalept for:

• Complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy

Approved in Canada as Myalept for:

• Complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy
• Patients with partial lipodystrophy

Who Is Running the Clinical Trial?

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Lead Sponsor

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

The MEASuRE registry is collecting long-term safety and effectiveness data on metreleptin, a treatment for metabolic complications in patients with lipodystrophy, involving 85 patients from 15 US and 4 EU sites as of October 2022.

The integration of MEASuRE with the existing European Registry of Lipodystrophies (ECLip) has allowed for efficient data collection and validation, demonstrating that collaboration can enhance patient enrollment and streamline data gathering for new registries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Metreleptin Effectiveness and Safety Registry (MEASuRE): concept, design and challenges. Haymond, MW., Araújo-Vilar, D., Balser, J., et al.[2023]

Metreleptin, a synthetic leptin analog, has been approved by the FDA for treating generalized lipodystrophy and has shown significant efficacy in reversing severe metabolic complications like hyperglycemia and fatty liver disease in patients with leptin deficiency.

While metreleptin is generally safe for daily subcutaneous administration, there are concerns about potential immune complications, such as lymphoma, and further research is needed to understand its long-term effects and the development of anti-leptin antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New advances in the treatment of generalized lipodystrophy: role of metreleptin. Rodriguez, AJ., Mastronardi, CA., Paz-Filho, GJ.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT00085982

Effect of Metreleptin Therapy in the Treatment of Severe ... Primary Objective: To determine if 1 year of metreleptin will improve glycemia control in patients with genetic defects of the insulin receptor. Secondary ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30805888/

Long-term effectiveness and safety of metreleptin in ... - PubMed In patients with PL, treatment with metreleptin was well tolerated and resulted in improvements in glycemic control, hypertriglyceridemia, and liver volume.

3. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.14726

Therapeutic indications and metabolic effects of metreleptin in ... We first analysed the metreleptin response in all patients with LD (Table S3). After short-term metreleptin therapy, LD patients lost weight, ...

4. aetna.com aetna.com/cpb/medical/data/800_899/0882.html?ref=counterforcehealth.org

Metreleptin (Myalept) - Medical Clinical Policy Bulletins Metreleptin may help improve the lipoprotein profile, insulin sensitivity, and quality of life (QOL) of patients with TBI-related lipodystrophy. In a single- ...

5. academic.oup.com academic.oup.com/jes/article/5/4/bvab019/6139135

Effects of Metreleptin on Patient Outcomes and Quality of Life ... This study demonstrates that metreleptin is associated with meaningful clinical and quality-of-life improvements.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10214317/

The Metreleptin Effectiveness and Safety Registry (MEASuRE) MEASuRE (Metreleptin Effectiveness And Safety Registry) is a post-authorization, voluntary registry that gathers long-term safety and effectiveness data on ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2015/125390s010lbl.pdf

MYALEPT® (metreleptin) for injection for subcutaneous use The safety of MYALEPT ... Clinical studies in patients with generalized lipodystrophy suggest that MYALEPT increases insulin sensitivity and reduces food intake.

8. myalept.com myalept.com/hcp/safety

Safety | Myalept® (metreleptin) for injection | HCP Most common adverse reactions (≥10%) in clinical trials were headache, hypoglycemia, decreased weight, and abdominal pain.

9. molinahealthcare.com molinahealthcare.com/-/media/Molina/PublicWebsite/PDF/Providers/common/pa-criteria/Myalept-metreleptin-C17341-A.pdf

Myalept (metreleptin) C17341-A There are serious safety concerns associated with Myalept. Myalept has two Boxed Warnings related to the risk of lymphoma and the risk of ...