Recruiting
Early Phase 1

GLP-1Ra with Teplizumab

Sponsor:

Vanderbilt University Medical Center

Code:

NCT06338553

Conditions

Type 1 Diabetes

Eligibility Criteria

Sex: All

Age: 12 - 50

Healthy Volunteers: Not accepted

Interventions

Semaglutide (Rybelsus®)

Placebo

Study Details

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

Study ID

NCT06338553

Start date

Jun 12, 2024

Status verified date

Dec, 2025

Completion date

Mar, 2027

Anticipated

Primary completion date

Mar, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 12 - 50

Healthy Volunteers: Not accepted

Aims 1-3: Stage 2 T1DM with TZIELD® and GLP-1Ra

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)

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

Aim 4: Early Stage 3 T1DM with GLP-1Ra Monotherapy Inclusion Criteria

  • 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

  • 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

Study Design

Enrollment

24 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

placebo comparator: 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.

experimental: 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.

placebo comparator: Placebo Comparator: Participants receiving placebo, Stage 3 T1DM participants

Participants receive a placebo orally once before each MMTT.

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

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

Interventions

Semaglutide (Rybelsus®)

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

Placebo

placebo capsule or tablet once before each MMTT.

Primary outcome measure

  • Investigate the impact of GLP-1Ra on postprandial glycemia in a pilot study [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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. [ Time Frame: 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 ]

Central Contacts and Locations

Central contacts

Daniel J Moore, MD, PhD

(615) 322- 7427metabolism@vumc.org

Wendi Welch, CCRP

metabolism@vumc.org

Locations

Vanderbilt University Medical Center

Recruiting

Nashville, Tennessee, United States, 37232

Contacts

Daniel J Moore, MD, PhD

(615) 322- 7427metabolism@vumc.org

Wendi Welch, CCRP

metabolism@vumc.org

Principal Investigator:

Daniel J Moore, MD, PhD

More Information

Sponsor

Vanderbilt University Medical Center

Last update posted

Dec 18, 2025

Last verified

Dec, 2025

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Vanderbilt University Medical Center on 2025-12-18.