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.
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
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
15
Study participants will be randomized to either placebo or semaglutide treatment for 12 months
Randomized to either placebo or semaglutide.
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
C-peptide area under the curve
measured levels of c-peptide during oral glucose tolerance test
Time frame: 12 months
C-peptide area under the curve (AUC)
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.
Time frame: 12 months
Stimulated incretin levels
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.
Time frame: 12 months
Glucagon secretion
Glucagon secretion in response to oral glucose tolerance test will be measured and compared at baseline and after treatment.
Time frame: 12 months
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