Semaglutide for Early Type 1 Diabetes

(GLP-TEP Trial)

Overseen By Wendi Welch, CCRP

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

Trial Summary

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.

What data supports the effectiveness of the drug Semaglutide for early type 1 diabetes?

Semaglutide has been shown to effectively lower blood sugar levels and body weight in people with type 2 diabetes, which suggests it might help manage blood sugar in early type 1 diabetes as well. It works by stimulating insulin release, which is important for controlling blood sugar. ^{1 2 3 4 5}

Is semaglutide safe for humans?

Semaglutide, used under names like Rybelsus and Ozempic, has been tested in many people with type 2 diabetes and is generally considered safe. It has a safety profile similar to other drugs in its class and has been shown to be safe for the heart in high-risk patients. ^{2 4 6 7 8}

How is the drug semaglutide unique for treating early type 1 diabetes?

Semaglutide is unique because it is a GLP-1 receptor agonist (a type of drug that mimics a hormone to stimulate insulin release) that is typically used for type 2 diabetes and obesity, but is now being explored for early type 1 diabetes. It is administered once weekly via injection, which is less frequent than many other diabetes treatments. ^{1 2 5 7 8}

What is the purpose of this trial?

The goal of this study is to determine how a drug class called glucagon-like peptide-1 receptor agonists (GLP-1Ra) affects people during an early stage of Type 1 Diabetes undergoing clinical teplizumab treatment. This study involves giving participants a liquid meal under different conditions and observing how their bodies respond, focusing on blood sugar levels, insulin effectiveness, and blood vessel function. The meal tests are followed by two post-treatment tests, one with the GLP-1Ra drug and the other with a placebo. Each test involves blood draws before and during the meal test, GLP-1Ra or placebo administration, and an ultrasound to measure blood vessel function. The goal is to see if GLP-1Ra can help manage blood sugar levels and improve cardiovascular health in this population.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 (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]

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, 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]

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, 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]

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]

References

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

Efficacy, safety, and patient satisfaction with oral semaglutide: first single-centre clinical experience. [2023]

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

Semaglutide: First Global Approval. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral semaglutide by subgroups of patient characteristics in the PIONEER phase 3 programme. [2022]

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

Semaglutide Is a New Once-Daily Oral Medication to Treat Type 2 Diabetes. [2021]

5. England 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. [2022]

6. Belgium pubmed.ncbi.nlm.nih.gov

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

7. Japan pubmed.ncbi.nlm.nih.gov

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

8. Belgium pubmed.ncbi.nlm.nih.gov

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