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Not yet recruiting NCT07430332

GLP-1 RA for Stage 1 Type 1 Diabetes

Phase II Interventional Stage 1 Diabetes Mellitus, Type 1

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Semaglutide, Placebo.
Who it may be relevant to
Registry conditions: Stage 1 Diabetes Mellitus, Type 1. Basic parameters: 12 years — 70 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Official title

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

Overview

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.

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.

Interventions

  • Drug Semaglutide
    Study participants will be randomized to either placebo or semaglutide treatment for 12 months
  • Drug Placebo
    Randomized to either placebo or semaglutide.

Primary outcome measures

  • C-peptide area under the curve [Time frame: 12 months]
  • C-peptide area under the curve (AUC) [Time frame: 12 months]
Secondary outcome measures (2)
  • Stimulated incretin levels [Time frame: 12 months]
  • Glucagon secretion [Time frame: 12 months]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Triple blind
Primary purpose
Prevention

Study locations

United States · 1 center
  • Cincinnati Children's Hospital Medical Center — Cincinnati

Publications

  • Yesildag B, Mir-Coll J, Neelakandhan A, Gibson CB, Perdue NR, Rufer C, Karsai M, Biernath A, Forschler F, Jin PW, Misun PM, Title A, Hierlemann A, Kreiner FF, Wesley JD, von Herrath MG. Liraglutide protects beta-cells in novel human islet spheroid models of type 1 diabetes. Clin Immunol. 2022 Nov;244:109118. doi: 10.1016/j.clim.2022.109118. Epub 2022 Sep 6. PMID 36084852
  • von Herrath M, Bain SC, Bode B, Clausen JO, Coppieters K, Gaysina L, Gumprecht J, Hansen TK, Mathieu C, Morales C, Mosenzon O, Segel S, Tsoukas G, Pieber TR; Anti-IL-21-liraglutide Study Group investigators and contributors. Anti-interleukin-21 antibody and liraglutide for the preservation of beta-cell function in adults with recent-onset type 1 diabetes: a randomised, double-blind, placebo-contro PMID 33662334

Identifiers

NCT: NCT07430332 · 2026-0116

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗