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

NCT06338553 | Recruiting Early Phase 1 DMC FDA Drug

• 2 other identifiers: 231620R01DK139322
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Type 1 Diabetes

Keywords

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

Outcome Measures

Primary Outcomes (4)

• Investigate the impact of GLP-1Ra on postprandial glycemia in a pilot study

  Researchers will measure postprandial glycemia during an MMTT before TZIELD® treatment. After TZIELD®, the effects of placebo versus semaglutide (Rybelsus®),a GLP-1Ra, will be compared.

  During the MMTT in which the participant is randomly selected to receive semaglutide (Rybelsus®), glucose level will be checked at timepoints -30, -15, 0, 10, 20, 30, 60, 90, 120, 150, 180, and 240 minutes

• Study the impact of GLP-1Ra on the disposition index (DI) in a pilot study

  Researchers will use the oral glucose minimal model to measure DI during an MMTT before and after TZIELD® treatment, comparing the effects of placebo versus Rybelsus®. As an exploratory outcome, β-cell endoplasmic reticulum dysfunction will be determined by measuring the proinsulin-to-C-peptide ratio during the MMTT.

  Based on the glucose and insulin readings obtained at timepoints -30, -15, 0, 10, 20, 30, 60, 90, 120, 150, 180, and 240 min and calculated approximately 1 month following completion of the MMTT once insulin levels in plasma are resulted.

• Determine the impact of GLP-1Ra on endothelial function in a pilot study

  B-mode ultrasound will be used 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, researchers aim to illuminate how GLP-1Ra may mitigate early vascular disease progression.

  During the last 30 minutes of each MMTT, between the 210 and 240 timepoints

• Determine how much GLP-1Ra monotherapy therapy changes the disposition index (DI) in a pilot study of early stage 3 T1DM.

  Researchers will assess the independent effects of GLP-1Ra on the disposition index (DI) by comparing the results between the GLP-1Ra and placebo conditions during four mixed meal tolerance tests (MMTTs): two at baseline shortly after diagnosis and two after a six-month interval.

  During the MMTT in which the participant is randomly selected to receive semaglutide (Rybelsus®), glucose level will be checked at timepoints -30, -15, 0, 10, 20, 30, 60, 90, 120, 150, 180, and 240 minutes

Study Arms (4)

Participants receiving placebo, Stage 2 T1DM participants

PLACEBO COMPARATOR

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.

Drug: Placebo

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

EXPERIMENTAL

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

Drug: Semaglutide (Rybelsus®)

Placebo Comparator: Participants receiving placebo, Stage 3 T1DM participants

PLACEBO COMPARATOR

Participants receive a placebo orally once before each MMTT.

Drug: Placebo

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

EXPERIMENTAL

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

Drug: Semaglutide (Rybelsus®)

Interventions

Semaglutide (Rybelsus®) DRUG

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

Experimental: Participants receiving a semaglutide (Rybelsus®), Stage 3 T1DM participants; Participants receiving a semaglutide (Rybelsus®), Stage 2 T1DM participants

Placebo DRUG

placebo capsule or tablet once before each MMTT.

Participants receiving placebo, Stage 2 T1DM participants; Placebo Comparator: Participants receiving placebo, Stage 3 T1DM participants

Eligibility Criteria

• Age: 12 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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
• 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
• DKA history: history of diabetic ketoacidosis requiring hospital admission

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Central Study Contacts

Daniel J Moore, MD, PhD

CONTACT

(615) 322- 7427; metabolism@vumc.org

Wendi Welch, CCRP

CONTACT

metabolism@vumc.org

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pediatrics, Division of Pediatric Endocrinology and Diabetes

Model Details: 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.

Study Record Dates

• First Submitted: March 7, 2024
• First Posted: March 29, 2024
• Study Start: June 12, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.
• Access Criteria: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA).

Locations

US (1)