MedDataX Logo

GLP-1Ra Impact on Metabolic Outcomes in Stage 2 T1DM While Receiving Teplizumab

NCT ID: NCT06338553

Last Updated: 2025-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

EARLY_PHASE1

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-06-12

Study Completion Date

2027-03-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The long-term goal is to determine whether repurposing GLP-1Ra for stage 2 in combination with immunotherapy can modify the disease course, reducing the need for exogenous insulin therapy and leading to improved cardiometabolic outcomes and quality of life. For early stage 3 T1DM, we aim to determine whether GLP-1Ra can offer similar protective effects in preserving β-cell function and stabilizing glycemic control.

The immediate objective is to investigate the impact of GLP-1Ra's insulinotropic and glucagonostatic effects on dysmetabolism in stage 2 and early stage 3 T1DM. The study hypothesizes that these effects will each delay the need for exogenous insulin by improving three key aspects of dysmetabolism: 1) postprandial glycemia, 2) disposition index (i.e., the ability of the islet cells to compensate for a given insulin sensitivity), and 3) endothelial function. The rationale for this hypothesis is based on two observations: first, GLP-1Ra combined with immunomodulatory therapy sustains endogenous secretion in response to a mixed meal tolerance test (MMTT) during the first year of stage 3; and second, GLP-1Ras mitigate postprandial hyperglucagonemia in longer-duration T1DM. To test the hypothesis, studies will be conduct in individuals with stage 2 T1DM treated with teplizumab using a crossover design structured around the following specific aims:

Aim 1: Investigate the impact of GLP-1Ra on postprandial glycemia in a pilot study. The study team will measure postprandial glycemia during an MMTT before teplizumab treatment. After teplizumab the study team will compare the effects of placebo versus semaglutide (a GLP-1Ra).

Aim 2: Study the impact of GLP-1Ra on the disposition index (DI) in a pilot study. The study team will use the oral glucose minimal model to measure DI during an MMTT before and after teplizumab treatment, comparing the effects of placebo versus semaglutide. As an exploratory outcome, β-cell endoplasmic reticulum dysfunction will be quantified by measuring the proinsulin-to-C-peptide ratio during the MMTT.

Aim 3: Determine the impact of GLP-1Ra on endothelial function in a pilot study. The study team will use B-mode ultrasound to measure flow mediated vasodilation (FMD), a bioassay of endothelial function, during each MMTT. Because endothelial cells are often among the first affected by hyperglycemia and insulin resistance, the study aims to illuminate how GLP-1Ra may mitigate early vascular disease progression.

And in a pilot study of early stage 3 T1DM, 4) GLP-1 Receptor Agonists. Aim 4: Determine how much GLP-1Ra monotherapy therapy changes the disposition index (DI) in a pilot study of early stage 3 T1DM.

Despite the promise of TZIELD®, the medication is not currently approved for patients with stage 3 T1DM. Thus, individuals who progress into stage 3 T1DM continue to face significant challenges, including loss of β-cell function and the need for exogenous insulin. As patients move into stage 3, there is an opportunity for metabolic interventions that may preserve residual insulin production and mitigate the long-term impact of hyperglycemia. Accordingly, we will conduct a randomized, double-blind, placebo-controlled crossover study involving patients with early stage 3 T1DM. Each participant will undergo four mixed meal tolerance tests (MMTTs): two at baseline shortly after diagnosis and two after a six-month interval. During each MMTT, participants will receive either a single dose of GLP-1Ra (oral semaglutide) or placebo in a randomized order. This design allows us to assess the independent effects of GLP-1Ra on the disposition index (DI) by comparing the results between the GLP-1Ra and placebo conditions at both time points. By evaluating changes in DI and other metabolic parameters over time, we aim to determine how GLP-1Ra monotherapy influences β-cell function and insulin sensitivity in early stage 3 T1DM.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Type 1 Diabetes

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Type 1 Diabetes Stage 2 Type 1 Diabetes Early Stage Type 1 Diabetes GLP1-Ra Rybelsus mixed meal tolerance test (MMTT) Stage 3 Type 1 Diabetes

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

In this study, participants with stage 2 T1DM undergoing Teplizumab treatment will be randomly assigned to receive single doses of either a GLP-1Ra (oral semaglutide, Rybelsus®) or a placebo, and three separate Mixed Meal Tolerance Test (MMTT) tests, 3-5 months apart, will be conducted to assess the effects on blood sugar levels, insulin function, and vascular health.

Participants with early stage 3 T1DM will undergo four MMTT studies: two at baseline shortly after diagnosis and two after a six-month interval. During each pair of studies, participants will receive a single dose of GLP-1Ra (oral semaglutide, Rybelsus®) in one study and placebo in the other, with the order randomized to minimize potential sequencing effects. This approach allows us to assess the effects of GLP-1Ra on metabolic parameters and β-cell function at two critical time points in disease progression, shortly after diagnosis and after a six-month interval.
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
For applicable participants, a placebo will be given prior to a pre-TZIELD® meal test. For participants who have already received Teplizumab (TZIELD®) or those who are progressing to the 2 remaining study visits, a GLP-1Ra or placebo will be given in random orders at these two visits. The GLP-1Ra will only be given one time.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Participants receiving placebo, Stage 2 T1DM participants

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 Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

placebo capsule or tablet once before each MMTT.

Participants receiving a semaglutide (Rybelsus®), Stage 2 T1DM participants

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

Group Type EXPERIMENTAL

Semaglutide (Rybelsus®)

Intervention Type DRUG

7 mg single dose of Rybelsus® by mouth once before each MMTT

Placebo Comparator: Participants receiving placebo, Stage 3 T1DM participants

Participants receive a placebo orally once before each MMTT.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

placebo capsule or tablet once before each MMTT.

Experimental: Participants receiving a semaglutide (Rybelsus®), Stage 3 T1DM participants

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

Group Type EXPERIMENTAL

Semaglutide (Rybelsus®)

Intervention Type DRUG

7 mg single dose of Rybelsus® by mouth once before each MMTT

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Semaglutide (Rybelsus®)

7 mg single dose of Rybelsus® by mouth once before each MMTT

Intervention Type DRUG

Placebo

placebo capsule or tablet once before each MMTT.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Age: 12-50 years
* BMI: 18-31 kg/m2 (adults) or 5-95th %ile (pediatric)
* Stage 2 T1DM (i.e., ≥ 2 islet auto-antibodies and:
* fasting glucose ≥ 100 mg/dL and \< 126 mg/dL OR
* 2-hr OGTT /MMTT ≥ 140 mg/dL and \< 200 mg/dL OR
* During an OGTT having a glucose of \> 199 mg/dL at 30, 60, or 90 minutes)


* Age: 12-50 years
* BMI: 18-31 kg/m2 (adults) or 5-95th %ile (pediatric)
* Early stage 3 T1DM with either
* HbA1c 6.5% to 8.0% at diagnosis OR
* HbA1c 5.7% to 6.4% with oral glucose test meeting ADA criteria for stage 3 T1DM within the past three months prior to or during screening visit
* Time of stage 3 diagnosis: within eight weeks of first study visit

Exclusion Criteria

* 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
* Medications: Any diabetes medication, any antioxidant vitamin supplement (\<2 weeks before a study), any systemic glucocorticoid, antipsychotic, atenolol, metoprolol, propranolol, niacin, any thiazide diuretic, any OCP with \> 35 mcg ethinyl estradiol, growth hormone, any immunosuppressant, antihypertensive, any antihyperlipidemic
* Other: pregnancy, peri- or post-menopausal women, active smoker


* DKA history: history of diabetic ketoacidosis requiring hospital admission
* Comorbidities:
* Family history of medullary thyroid carcinoma
* Diagnosis of pancreatitis or gastroparesis within the past 3 years
* Medications: Any diabetes medication, any antioxidant vitamin supplement (\<2 weeks before a study), any systemic glucocorticoid, antipsychotic, atenolol, metoprolol, propranolol, niacin, any thiazide diuretic, any OCP with \> 35 mcg ethinyl estradiol, growth hormone, any immunosuppressant, antihypertensive, any antihyperlipidemic
* Other: pregnancy, peri- or post-menopausal women, active smoker
Minimum Eligible Age

12 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

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

NIH

Sponsor Role collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Daniel Moore

Associate Professor of Pediatrics, Division of Pediatric Endocrinology and Diabetes

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United States

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Daniel J Moore, MD, PhD

Role: CONTACT

Phone: (615) 322- 7427

Email: [email protected]

Wendi Welch, CCRP

Role: CONTACT

Email: [email protected]

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Daniel J Moore, MD, PhD

Role: primary

Wendi Welch, CCRP

Role: backup

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

R01DK139322

Identifier Type: NIH

Identifier Source: secondary_id

View Link

231620

Identifier Type: -

Identifier Source: org_study_id