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)

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

11 Participants Needed

Trial Summary

What is the purpose of this trial?

Study Description: Patients with mutations of the insulin receptor have diabetes that is challenging to control with conventional therapies, leading to early morbidity and mortality. We hypothesize that recombinant leptin (metreleptin) in these patients will improve glycemia control. Objectives: Primary Objective: To determine if 1 year of metreleptin will improve glycemia control in patients with genetic defects of the insulin receptor. Secondary Objectives: To determine mechanisms by which metreleptin improves glycemia. Endpoints: Primary Endpoint: Hemoglobin A1c. Secondary Endpoints: fasting plasma glucose, fasting insulin/C-peptide, glucose/insulin/C-peptide area under the curve during oral glucose tolerance test. Study Population: 20 male or female patients with mutations of the insulin receptor, age (Bullet)5 years, at the NIH Clinical Center. Description of Sites/Facilities Enrolling Participants: Description of Study Intervention: NIH Clinical Center Open label study of metreleptin, 0.2 mg/kg/day (max dose 0.24 mg/kg/day).

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.

What data supports the effectiveness of the drug Metreleptin for insulin resistance?

Metreleptin, a synthetic version of the hormone leptin, has been shown to improve insulin resistance and other metabolic issues in patients with lipodystrophy, a condition where the body lacks fat tissue. It has been effective in improving glucose and lipid levels, which are often problematic in these patients. ^{1 2 3 4 5}

How does the drug Metreleptin differ from other treatments for insulin resistance?

Metreleptin is unique because it is a hormone replacement therapy that can improve insulin resistance by promoting satiety (feeling full) and enhancing fat breakdown through the central nervous system. Unlike other treatments, it is administered subcutaneously (under the skin) and is particularly effective when combined with SGLT2 inhibitors, which help lower blood sugar by increasing glucose excretion through urine. ^{6 7 8 9 10}

Research Team

Rebecca J Brown, M.D.

Principal Investigator

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. England pubmed.ncbi.nlm.nih.gov

The Metreleptin Effectiveness and Safety Registry (MEASuRE): concept, design and challenges. [2023]

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

Immunogenicity associated with metreleptin treatment in patients with obesity or lipodystrophy. [2019]

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

New advances in the treatment of generalized lipodystrophy: role of metreleptin. [2022]

4. Japan pubmed.ncbi.nlm.nih.gov

Metreleptin treatment for congenital generalized lipodystrophy type 4 (CGL4): a case report. [2020]

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

Metreleptin: first global approval. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Case Report: Metreleptin and SGLT2 Inhibitor Combination Therapy Is Effective for Acquired Incomplete Lipodystrophy. [2021]

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

Teneligliptin, a Chemotype Prolyl-Thiazolidine-Based Novel Dipeptidyl Peptidase-4 Inhibitor with Insulin Sensitizing Properties. [2022]

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

Teneligliptin: a review in type 2 diabetes. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Adherence with metreleptin therapy and health self-perception in patients with lipodystrophic syndromes. [2020]

10. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Linagliptin: a novel methylxanthin based approved dipeptidyl peptidase-4 inhibitor. [2019]