Pegvisomant for Insulin Resistance

Overseen By Megan S Startzell, R.N.

Age: 18+

Sex: Any

Trial Phase: Phase 2

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

Must not be taking: Niacin, Anticoagulants, NSAIDs, others

Disqualifiers: Pregnancy, Liver disease, Triglycerides, 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: 4

Duration: 1 month

25 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: Lipodystrophy (LD) syndromes are a group of rare disorders that affect how a person s body can store and use fat tissue. Many people with LDs become severely insulin resistant. Some people are insulin resistant because of a variant in the insulin receptor gene. Insulin resistance causes many health problems. Objective: To learn if blocking the effects of growth hormone in the body will help people with severe insulin resistance. Eligibility: Adults aged 18 to 65 years with either a known variant in the insulin receptor gene or with a diagnosis of partial LD. Design: Participants will have 2 hospital stays, about 1 month apart. Each stay will be 3 or 4 nights. During each hospital stay, participants will have many tests. They will have a physical exam with blood tests. They will have all of their urine collected for a 24-hour period. They will have scans to measure their muscle, bone, and fat tissues. They will have tests to measure metabolism and insulin sensitivity. They may have an optional biopsy of fat tissue. During the first hospital visit, participants will learn how to give themselves shots of a drug (pegvisomant) that blocks growth hormone. The drug is injected under the skin. Participants will continue to give themselves these shots once a day at home. After the first hospital visit, participants will talk on the phone with members of the study team once each week. After 2 weeks they will have blood drawn for tests. Participants will stop the shots after the second hospital visit.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as niacin or drugs affecting fat breakdown, at least 8 weeks before joining. You also need to avoid changing diabetes or cholesterol medications within 2 weeks before starting. If you take blood thinners or certain pain relievers, you may not be eligible.

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

Pegvisomant is unique because it is a growth hormone receptor antagonist, which means it blocks the action of growth hormone, potentially improving insulin sensitivity. This mechanism is different from other treatments like metformin or thiazolidinediones, which primarily work by improving insulin sensitivity directly or through other pathways. ^{1 2 3 4 5}

Research Team

Rebecca J Brown, M.D.

Principal Investigator

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

Eligibility Criteria

Adults aged 18-65 with severe insulin resistance due to a variant in the insulin receptor gene or partial lipodystrophy can join. They must have completed puberty, not be on blood thinners, pregnant, or breastfeeding. Participants need to use contraception and cannot have certain medical conditions like significant liver disease.

Inclusion Criteria

I have a genetic variant affecting insulin or diagnosed with partial lipodystrophy.

I am between 18 and 65 years old.

I have finished growing and gone through puberty.

Exclusion Criteria

I haven't taken NSAIDs like aspirin or ibuprofen 2 weeks before my planned biopsy.

I am willing and able to sign the consent form.

I am a man who can father children and agree to use contraception during and 1 month after the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pegvisomant injections daily for 1 month to block growth hormone effects

1 month

2 hospital stays, each 3-4 nights

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Weekly phone calls, blood tests after 2 weeks

Treatment Details

Interventions

• Pegvisomant

Trial Overview The trial is testing Pegvisomant, a drug that blocks growth hormone effects in those with severe insulin resistance from lipodystrophy syndromes. It involves two hospital stays for tests and daily self-administered shots of Pegvisomant between visits.

Participant Groups

Group I: 1 Experimental Treatment 1 Intervention

open label pegvisomant

Pegvisomant is already approved in United States, European Union for the following indications:

Approved in United States as Somavert for:

• Acromegaly

Approved in European Union as Somavert for:

• Acromegaly

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

In Phase 2 trials involving 288 patients with type 2 diabetes and 137 with type 1 diabetes, the basal insulin analogue LY2605541 was associated with significant weight loss compared to insulin glargine, with 56.9% of T2DM and 66.1% of T1DM patients experiencing weight loss.

LY2605541 treatment led to a higher percentage of patients achieving ≥5% weight loss compared to glargine (4.8% vs. 0% in T2DM and 11.9% vs. 0.8% in T1DM), indicating its potential as a weight-neutral or weight-reducing insulin option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contrasting weight changes with LY2605541, a novel long-acting insulin, and insulin glargine despite similar improved glycaemic control in T1DM and T2DM. Jacober, SJ., Rosenstock, J., Bergenstal, RM., et al.[2022]

Basal insulin peglispro (BIL) shows a prolonged duration of action and reduced clearance compared to insulin lispro, making it potentially more effective for managing diabetes, as demonstrated in studies with diabetic rats.

BIL has a greater selectivity for the human insulin receptor and exhibits reduced mitogenic potential, suggesting it may have a safer profile regarding unwanted cell growth compared to other insulins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vivo and In Vitro Characterization of Basal Insulin Peglispro: A Novel Insulin Analog. Owens, RA., Hansen, RJ., Kahl, SD., et al.[2018]

Insulin resistance, influenced by genetics and lifestyle factors like diet and exercise, is a significant risk factor for cardiovascular disease and is closely linked to metabolic syndrome.

Lifestyle changes can positively impact insulin resistance, and medications like metformin and thiazolidinediones are effective treatments, with ongoing research into new drugs that target insulin sensitivity to improve overall health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Insulin sensitizers]. Scheen, AJ., Paquot, N.[2015]

In a 12-week study involving 21 patients with poorly controlled type 2 diabetes, replacing metformin with pioglitazone did not significantly change HbA1c or fasting plasma glucose levels, indicating limited efficacy in glycemic control for the overall group.

However, the treatment led to significant improvements in triglycerides, HDL cholesterol, serum adiponectin, and arterial stiffness, suggesting potential cardiovascular benefits despite the lack of change in blood sugar levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of replacing metformin with pioglitazone on glycemic control in japanese patients with poorly controlled type 2 diabetes mellitus: A 12-week, open-label, prospective study. Sakaue, S., Kamigaki, M., Yoshimura, H., et al.[2021]

In a study involving 36 Chinese patients with type 2 diabetes, PB-119, a once-weekly injection, significantly improved beta-cell function and insulin resistance after 12 weeks of treatment.

High-dose PB-119 led to better outcomes in insulin sensitivity and beta-cell function compared to baseline, indicating its potential as an effective antidiabetic therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PEGylated exenatide injection (PB-119) improves beta-cell function and insulin resistance in treatment-naïve type 2 diabetes mellitus patients. Liu, X., Song, L., Zhang, Y., et al.[2023]

References

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

Contrasting weight changes with LY2605541, a novel long-acting insulin, and insulin glargine despite similar improved glycaemic control in T1DM and T2DM. [2022]

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

In Vivo and In Vitro Characterization of Basal Insulin Peglispro: A Novel Insulin Analog. [2018]

3. Belgium pubmed.ncbi.nlm.nih.gov

[Insulin sensitizers]. [2015]

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

Effects of replacing metformin with pioglitazone on glycemic control in japanese patients with poorly controlled type 2 diabetes mellitus: A 12-week, open-label, prospective study. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

PEGylated exenatide injection (PB-119) improves beta-cell function and insulin resistance in treatment-naïve type 2 diabetes mellitus patients. [2023]