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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether pegvisomant, a drug that blocks growth hormone, can aid those with severe insulin resistance. This condition often affects individuals with certain rare genetic issues or a disorder called partial lipodystrophy, which alters fat storage in the body. Participants will stay in the hospital twice for a few days each time to undergo tests and learn how to administer daily injections of the drug at home. Ideal candidates are adults diagnosed with partial lipodystrophy or those with a known gene variant causing insulin resistance. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that pegvisomant has been studied for over ten years with more than 2,000 patients. Most people tolerated it well, experiencing no serious side effects. Some reported mild side effects, such as reactions at the injection site.

Studies also show that pegvisomant effectively lowers certain hormone levels in patients with conditions like acromegaly, where the body produces too much growth hormone. Long-term research suggests it is a safe treatment option for these conditions.

This trial is in phase 2, indicating that earlier research demonstrated some safety. However, more information is needed to understand all possible effects. Prospective participants should discuss any concerns with the study team or their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pegvisomant is unique because it targets insulin resistance by blocking the action of growth hormone, which can improve insulin sensitivity. Most treatments for insulin resistance, like metformin or lifestyle modifications, work by enhancing insulin action or reducing glucose production. Pegvisomant offers a novel mechanism of action by specifically inhibiting growth hormone receptors, which is different from how standard treatments work. Researchers are excited about this approach because it could provide a new way to manage insulin resistance, particularly for individuals who do not respond well to traditional therapies.

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

Research has shown that pegvisomant, a drug that blocks growth hormone, can improve the body's insulin use. In previous studies, participants taking pegvisomant demonstrated better insulin sensitivity, meaning their bodies used insulin more effectively. For patients with acromegaly, a condition characterized by excessive growth hormone production, pegvisomant reduced insulin resistance and enhanced insulin function overall. This trial will evaluate pegvisomant's potential benefits for individuals with severe insulin resistance, such as those with lipodystrophy. The drug's ability to block growth hormone is crucial to these potential benefits. ^{1 2 6 7 8}

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?

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 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.

Known allergic reactions pegvisomant or any of its components.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8428076/

More than a decade of real-world experience of pegvisomant ... The main endpoints were long-term safety (comorbidities, adverse events (AEs), pituitary tumour volumes, liver tests) and efficacy (IGF1 changes). Results.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1096637402000837

Growth hormone receptor antagonist improves insulin ... Weight remained stable throughout the study. The results show that the Pegvisomant is an effective agent for improving insulin resistance in subjects who ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6420440/

Diabetes in patients with acromegaly treated with pegvisomant Medical treatment modalities for acromegaly may in turn reduce insulin resistance and increase insulin sensitivity [7]. These treatments include somatostatin ...

4. somavert.pfizerpro.com somavert.pfizerpro.com/decades-of-results

Decades of Results Publication of data for 710 patients who received SOMAVERT monotherapy ... A comparison of the effects of pegvisomant and octreotide on glucose, insulin ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05470504

Study of Growth Hormone Inhibition Using Pegvisomant in ... To learn if blocking the effects of growth hormone in the body will help people with severe insulin resistance.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4592912/

Long-term effects of pegvisomant on comorbidities in ... Results. At the first cardiac evaluation, 20±16 months after pegvisomant introduction, IGF1 levels normalized in 29 (69%) of the 42 patients. The ...

7. link.springer.com link.springer.com/article/10.1007/s11154-025-10002-9

Pegvisomant in managing comorbidities of acromegaly After 6, 12, and 18 months of treatment, mean IGF-I levels decreased by at least 50%, and 97% of patients treated for 12 months or longer ...

8. academic.oup.com academic.oup.com/jcem/article/99/10/3644/2836378

Long-Term Efficacy and Safety of Pegvisomant in ... The combination treatment with LA-SRIFs and PEGV was effective in 97% of the patients, it appears to be a safe medical treatment and it reduces the required ...