GLUCOSE-MGH: Genetic Links Understood Through Challenge With Oral Semaglutide Exposure at MGH
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: oral semaglutide, Mixed Meal Tolerance Test (MMTT).
- Who it may be relevant to
- Registry conditions: Genetic Predisposition, Metabolic Diseases, Type 2 Diabetes. Basic parameters: 18 years — 65 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 →
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Overview
The goal of this research study is to evaluate the pathophysiologic mechanisms by which genetic variation impacts response to an FDA-approved medication commonly used to treat type 2 diabetes called oral semaglutide (Rybelsus) and to characterize the physiological response to a mixed meal tolerance test (MMTT) before and after a 14-day treatment with oral semaglutide. The investigators will do this by measuring factors in the blood, such as sugars, fats, metabolites, and proteins, after eating a standardized breakfast meal at the first visit and after taking 14 doses of oral semaglutide over two weeks before the second study visit. The food (mixed meal breakfast) we will be studying is specially prepared to contain a set amount of protein, carbohydrates, and fat. The investigators hypothesize that understanding how the acute biochemical response to oral semaglutide differs by genetic variation will generate insight into drug mechanisms and type 2 diabetes pathophysiology.
Detailed description
On day 1 (Visit 1), the research subject will present to the Translational and Clinical Research Center (TCRC) after an overnight fast. We will obtain informed consent, check vital signs, take anthropometric measurements, and draw fasting blood work through an intravenous catheter. The subject will then be provided a standard mixed meal to be consumed within 30 minutes. Additional blood will be drawn at the time of meal completion (0 minutes), as well as 5, 15, 30, 60, 90, and 120 minutes following the meal. During study days 3-15, the subject will take 7 mg of oral semaglutide once daily. On day 16 (Visit 2), the research subject will return to the TCRC. During this visit, the subject will take the final (14th) dose of semaglutide, receive fasting blood work, and receive another mixed meal with subsequent blood draws at several time points over 120 minutes.
Interventions
- Drug oral semaglutide
Semaglutide is the only oral glucagon-like peptide 1 receptor agonist (GLP-1 RA) approved for treatment of type 2 diabetes. Participants will receive 7 mg of oral semaglutide once daily for 14 days in between Visit 1 and Visit 2. - Other Mixed Meal Tolerance Test (MMTT)
The MMTT is developed by the Metabolism and Nutrition Metabolic Kitchen at the MGH TCRC. The meal is a high-calorie, high-carbohydrate and moderate-to-high glycemic index challenge composed of commonly consumed breakfast food items. It provides nearly 90 grams of carbohydrates and mimics an oral glucose challenge. The participants will undergo a MMTT at Visit 1 and Visit 2.
Primary outcome measures
- Insulin response to oral semaglutide treatment [Time frame: 15 days]
Secondary outcome measures (3)
- Fasting glucose response to oral semaglutide treatment [Time frame: 15 days]
- Cumulative glucose response to oral semaglutide treatment [Time frame: 15 days]
- Baseline incretin level [Time frame: 120 minutes during Visit 1]
Eligibility criteria
Inclusion criteria
- Males or non-pregnant females
- Ages 18-65 (inclusive)
- Able/willing to give consent
- Span the metabolic range between normal glycemia and pre-diabetes (fasting glucose of 100-125 mg/dL based on chart review of existing laboratory data)
Exclusion criteria
- Currently taking medications or intending to take medications for diabetes
- Currently taking medications or intending to take medications that affect glycemic parameters, such as glucocorticoids, growth hormone, or fluoroquinolones
- Personal history of intestinal malabsorption, bariatric surgery, celiac disease, gallbladder disease, or pancreatitis
- Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2
- Estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 per the Modification of Diet in Renal Disease equation
- History of cirrhosis and/or aspartate aminotransferase or alanine aminotransferase more than 3x upper limit of normal
- Dietary restrictions preventing consumption of a MMTT
- Women who are pregnant, nursing, or at risk of becoming pregnant
- Participation in other interventional studies during the current study
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 1 center
- Massachusetts General Hospital — Boston
Identifiers
NCT: NCT06003153 · 2023P001852 · K23DK131345