GLP-1 RA for Stage 1 Type 1 Diabetes

February 18, 2026 updated by: Children's Hospital Medical Center, Cincinnati

Leveraging Semaglutide for Preservation of Beta Cell Function and Restoration of Alpha Cell Function

This study seeks to evaluate the hormone responses of insulin, c-peptide, glucagon, and incretins to semaglutide, a GLP-1 receptor agonist therapy, in individuals with stage 1 type 1 diabetes. The goal of this study is to see if semaglutide can protect beta cell function in this group of people and delay the progression to stage 2 type 1 diabetes.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This study aims to evaluate the effects of semaglutide on pancreatic beta and alpha cell function in individuals with stage 1 type 1 diabetes (T1D). Despite having euglycemia, individuals with stage 1 T1D may already exhibit loss of the first phase insulin response (FPIR). Incretins play a significant role in FPIR through their effects on insulin secretion and sensitivity, offering a potential therapeutic target for restoration of FPIR. Furthermore, prior studies have demonstrated that individuals with T1D exhibit inappropriate glucagon release in response to glucose, worsening glycemic control. Not only do incretins affect beta cells, but they can also inhibit glucagon secretion, potentially attenuating this dysregulated glucagon response. Studies have shown safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with T1D and their beneficial effects on reducing inflammation and preserving beta cell function. However, no studies have evaluated the effects of GLP-1 RAs on beta cell function and glucagon secretion in stage 1 type 1 diabetes to date. As incretins can inhibit glucagon secretion, we hypothesize that semaglutide may attenuate dysregulated glucagon responses, thereby improving glycemic control and potentially altering disease progression. To evaluate the effects of semaglutide in stage 1 T1D, we propose the following aims:

  1. Define the effect of semaglutide on beta cell function. We hypothesize that semaglutide may restore FPIR and preserve beta cell function. A 2 hour, 7-point oral glucose tolerance test (OGTT) at baseline and after 12 months of semaglutide will be used to evaluate FPIR and beta cell function through serial measurements of insulin, pro-insulin, C-peptide, glucose, GLP-1, and GIP.
  2. Identify the effect of semaglutide on glucagon secretion in response to glucose. We hypothesize that semaglutide will suppress glucose-stimulated glucagon release. We will evaluate this by measuring stimulated glucagon levels via a 2 hour, 7-point OGTT and by measuring pre and post OGTT liver glycogen content via liver MRI at baseline and after 12 months of semaglutide therapy.

Study Type

Interventional

Enrollment (Estimated)

15

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Stage 1 Type 1 Diabetes
  • Screening OGTT with impaired or loss of first phase insulin secretion but no dysglycemia to suggest stage 2 or stage 3 type 1 diabetes

Exclusion Criteria:

  • History of anaphylaxis or allergies to GLP-1 receptor agonists
  • Already on a GLP-1 receptor agonist
  • History of bariatric surgery
  • Personal or family history of cancer such as medullary thyroid cancer
  • Personal history of pancreatitis or pathogenic variants associated with increased risk of pancreatitis
  • Severe hypoglycemia within 3 months of study enrollment
  • Pregnant, breastfeeding, or the intention of becoming pregnant or not using adequate contraceptive measures
  • Adult individuals with BMI < 18.5 kg/m2 and pediatric participants with BMI < 5th percentile

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Semaglutide or Placebo Treatment
Drug: Semaglutide
Study participants will be randomized to either placebo or semaglutide treatment for 12 months
Placebo Comparator: Placebo
Randomized to placebo or semaglutide
Drug: Placebo
Randomized to either placebo or semaglutide.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
C-peptide area under the curve
Time Frame: 12 months
measured levels of c-peptide during oral glucose tolerance test
12 months
C-peptide area under the curve (AUC)
Time Frame: 12 months
C-peptide area under the curve levels will be calculated from stimulated C-peptide levels in an oral glucose tolerance test at baseline and after treatment with placebo or semaglutide.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Stimulated incretin levels
Time Frame: 12 months
Stimulated incretin levels will be measured via oral glucose tolerance test at baseline and after treatment. The time to peak level and peak level will be compared.
12 months
Glucagon secretion
Time Frame: 12 months
Glucagon secretion in response to oral glucose tolerance test will be measured and compared at baseline and after treatment.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Hospital Medical Center, Cincinnati

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 1, 2027

Primary Completion (Estimated)

June 1, 2029

Study Completion (Estimated)

January 1, 2030

Study Registration Dates

First Submitted

February 18, 2026

First Submitted That Met QC Criteria

February 18, 2026

First Posted (Actual)

February 24, 2026

Study Record Updates

Last Update Posted (Actual)

February 24, 2026

Last Update Submitted That Met QC Criteria

February 18, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2026-0116

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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