Semaglutide for Early Type 1 Diabetes

(GLP-TEP Trial)

Overseen By Justin M Gregory, MD, MSCI

Age: < 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Vanderbilt University Medical Center

Must not be taking: Diabetes meds, Antipsychotics, Antihypertensives, others

Disqualifiers: Hypertension, Kidney disease, Liver disease, others

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 4 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how semaglutide can manage blood sugar and improve heart health in individuals with early-stage Type 1 Diabetes. Participants will receive either semaglutide or a placebo, followed by a meal to observe their body's reaction. The goal is to understand the drug’s effect when used alongside teplizumab in controlling blood sugar and maintaining healthy blood vessels. Individuals with early-stage Type 1 Diabetes and conditions like high fasting blood sugar might be suitable for this trial. As an Early Phase 1 trial, this research seeks to understand how semaglutide works in people, offering participants a chance to be among the first to explore its potential benefits.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications before joining the trial. Specifically, you cannot take any diabetes medications, antioxidant vitamin supplements within 2 weeks before the study, or several other listed medications like systemic glucocorticoids, antipsychotics, and certain blood pressure and cholesterol medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that semaglutide, a pill, has been studied for safety in various situations. Although it hasn't been specifically tested in people with early-stage Type 1 Diabetes, some studies suggest it can lower the risk of heart problems in people with diabetes, indicating potential heart safety.

In some cases, semaglutide has been used for Type 1 Diabetes, despite not being officially approved for this use, and it has shown some benefits. However, it is generally not recommended for people with Type 1 Diabetes, so further research is needed to confirm its safety and effectiveness for them.

Ongoing studies are examining common side effects like low blood sugar and stomach issues. Since this trial is in an early phase, it focuses on basic safety and how well people tolerate the treatment. While the results are promising, more information is needed to fully understand semaglutide's safety for early-stage Type 1 Diabetes. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Type 1 Diabetes?

Unlike the standard care for early type 1 diabetes, which typically involves insulin therapy and lifestyle adjustments, semaglutide offers a novel approach. Semaglutide, marketed as Rybelsus®, is unique because it is an oral medication that mimics a natural hormone called GLP-1, which plays a role in blood sugar regulation. Most diabetes treatments focus on insulin replacement or sensitivity, but semaglutide works differently by enhancing insulin secretion and reducing glucose production. Researchers are excited about semaglutide because it could offer a convenient, once-daily oral option that may help manage blood sugar levels without the need for injections, potentially improving the quality of life for patients.

What evidence suggests that semaglutide might be an effective treatment for early Type 1 Diabetes?

Research shows that semaglutide, a type of medication, can help control blood sugar levels. In studies with people who have Type 2 diabetes, semaglutide improved blood sugar control and benefited heart health. Evidence also suggests it may aid in weight loss and reduce the need for insulin in people with Type 1 diabetes. This trial will evaluate semaglutide in participants with early Type 1 diabetes. Participants will receive semaglutide, which mimics a hormone that lowers blood sugar and can improve heart and blood vessel function. Although most research focuses on Type 2 diabetes, early findings suggest it might also help those with Type 1 diabetes manage their condition. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with early-stage Type 1 Diabetes (Stage 2) who are undergoing treatment with teplizumab. Participants should be able to undergo multiple meal tests and blood draws. Specific inclusion and exclusion criteria details were not provided.

Inclusion Criteria

BMI: 18-31 kg/m2 (adults) or 5-95th %ile (pediatric)

I am between 12 and 50 years old.

I have early-stage type 1 diabetes with specific blood sugar levels and antibodies.

Exclusion Criteria

Other: pregnancy, peri- or post-menopausal women, active smoker

Comorbidities: SBP > 140 mmHg and DBP > 100 mmHg, eGFR by MDRD equation of < 60 mL/min/1.73m2, AST or ALT > 2.5 times ULN, Family history of medullary thyroid carcinoma, Diagnosis of pancreatitis or gastroparesis within the past 3 years

I am not currently taking diabetes medication, high-dose vitamins, steroids, certain heart or mental health meds, water pills, specific birth control, growth hormones, or drugs for immune system, blood pressure, or cholesterol.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Treatment Assessment

Participants undergo a mixed meal tolerance test (MMTT) to measure baseline postprandial glycemia, disposition index, and endothelial function before teplizumab treatment

1 day

1 visit (in-person)

Treatment

Participants receive teplizumab treatment followed by post-treatment MMTTs with either placebo or semaglutide (GLP-1Ra) to assess metabolic outcomes

4 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on metabolic and cardiovascular outcomes

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Semaglutide

Trial Overview

The study is testing the effects of a GLP-1Ra drug, Semaglutide (Rybelsus®), compared to a placebo in managing blood sugar levels and cardiovascular health during teplizumab treatment for Type 1 Diabetes.

How Is the Trial Designed?

Group I: Participants receiving a semaglutide (Rybelsus®), Stage 2 T1DM participants Experimental Treatment 1 Intervention

Participants receive 7mg of semaglutide (Rybelsus®) orally once before one of the post-TZIELD® MMTTs. Rybelsus is only given one time.

Group II: Experimental: Participants receiving a semaglutide (Rybelsus®), Stage 3 T1DM participants Experimental Treatment 1 Intervention

Participants receive 7mg of semaglutide (Rybelsus®) orally once before each MMTT.

Group III: Participants receiving placebo, Stage 2 T1DM participants Placebo Group 1 Intervention

Participants receive a placebo orally once before the pre-TZIELD® MMTT. Participants also receive a placebo orally once before one of the post-TZIELD® MMTTs.

Group IV: Placebo Comparator: Participants receiving placebo, Stage 3 T1DM participants Placebo Group 1 Intervention

Participants receive a placebo orally once before each MMTT.

Semaglutide is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in United States as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in Canada as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in Japan as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in United States as Wegovy for:

• Obesity

Approved in United States as Rybelsus for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

Semaglutide, marketed as Rybelsus, is the first oral glucagon-like peptide receptor agonist approved by the FDA in 2019 for treating type 2 diabetes, highlighting its innovative delivery method.

This medication, taken once daily, aids in glucose control and weight management, potentially leading to improved health outcomes for individuals with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide Is a New Once-Daily Oral Medication to Treat Type 2 Diabetes. Blakely, KK., Weaver, K.[2021]

In a phase 3 trial involving 388 treatment-naive patients with type 2 diabetes, semaglutide significantly reduced HbA1c levels by 1.45% with 0.5 mg and 1.55% with 1.0 mg doses compared to placebo, indicating its efficacy in improving glycaemic control.

Semaglutide also led to significant weight loss, with reductions of 3.73 kg and 4.53 kg for the respective doses, while maintaining a safety profile similar to existing GLP-1 receptor agonists, with most adverse events being mild to moderate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. Sorli, C., Harashima, SI., Tsoukas, GM., et al.[2022]

In a study of 20 patients with type 2 diabetes in Slovenia, oral semaglutide significantly reduced HbA1c levels and fasting plasma glucose, indicating its efficacy in improving glycaemic control.

Patients reported high satisfaction with the treatment, and while some experienced mild gastrointestinal side effects, the overall safety profile was considered good, suggesting that oral semaglutide is a promising option for diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, safety, and patient satisfaction with oral semaglutide: first single-centre clinical experience. Janić, M., Jovanović, M., Janež, A., et al.[2023]

Semaglutide, a GLP-1 receptor agonist with a long half-life, effectively promotes insulin secretion in a glucose-dependent manner, making it a valuable treatment for type 2 diabetes, approved for use worldwide and in Japan since 2018.

Oral semaglutide (Rybelsus®) is the first GLP-1 receptor agonist available in pill form, showing continuous benefits in glycemic control for patients with type 2 diabetes across various stages, as demonstrated in multiple global clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New drug for type 2 diabetes: introduction of oral Semaglutide (Rybelsus&#174; tablets), an oral GLP-1 receptor agonist]. Miyasaka, K.[2022]

Oral semaglutide, particularly at doses of 14 mg or flexibly dosed, significantly reduced HbA1c levels and body weight in patients with type 2 diabetes compared to other treatments, especially in those with higher baseline HbA1c levels.

The safety profile of oral semaglutide was comparable to that of other treatments, although it was associated with a higher incidence of gastrointestinal adverse events, which were consistent across different patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral semaglutide by subgroups of patient characteristics in the PIONEER phase 3 programme. Aroda, VR., Bauer, R., Christiansen, E., et al.[2022]

Semaglutide (Ozempic®) is an effective once-weekly treatment for type 2 diabetes, showing superior glucose-lowering effects and greater weight loss compared to other GLP-1 receptor agonists in Phase III clinical trials.

It is approved for use in Belgium for patients with type 2 diabetes who have not achieved adequate control with other antidiabetic therapies, particularly in those with a body mass index of 30 kg/m² or higher.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Semaglutide, once weekly GLP-1 receptor agonist (Ozempic®)]. Scheen, AJ.[2019]

Oral semaglutide (Rybelsus®) has been shown to provide better glycaemic control and promote weight loss in patients with type 2 diabetes (T2DM) compared to standard oral glucose-lowering medications, based on data from the PIONEER clinical trial program involving 9543 patients.

The safety profile of oral semaglutide is similar to other GLP-1 receptor agonists, and it demonstrated cardiovascular safety comparable to placebo in high-risk patients, making it a viable option for T2DM management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus®)]. Paquot, N.[2022]

Semaglutide (Ozempic®) is a new subcutaneous treatment for type 2 diabetes that effectively lowers blood glucose levels by stimulating insulin release and also helps reduce body weight.

The once-weekly injection has been approved in the US, Puerto Rico, and Canada, and is also under review in other countries, with ongoing clinical development for additional conditions like obesity and liver diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide: First Global Approval. Dhillon, S.[2019]

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EFFICACY AND SAFETY OF ONCE WEEKLY ...

This study aims to investigate the long-term safety and effectiveness of semaglutide in obese patients with type 1 diabetes who are already on HCL therapy but ...