GLUCOSE-MGH: Genetic Links Understood Through Challenge With Oral Semaglutide Exposure at MGH
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18-65
SponsorMassachusetts General Hospital
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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)
Disqualifiers
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
Trial design
Design model
Single group
Treatments tested in this trial
oral semaglutide
DrugSemaglutide 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.
Mixed Meal Tolerance Test (MMTT)
Other interventionThe 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.
Treatment groups
125 Participants
are divided into 1 treatment groupGroup A: GLUCOSE-MGH StudyOther 2 interventions
Trial outcomes
Primary outcomes
1
Insulin response to oral semaglutide treatment
Investigators will measure the change in insulin area under the curve (AUC) over 120 minutes of the MMTT, calculated using the trapezoidal method, between Visit 1 and Visit 2 as an index of response to oral semaglutide, and compare this outcome by genotype at selected loci.
Time frame
15 daysSecondary outcomes
1
Fasting glucose response to oral semaglutide treatment
Investigators will measure the change in fasting glucose over 120 minutes of the MMTT, between the two visits, and compare this outcome by genotype at selected loci.
Time frame
15 days2
Cumulative glucose response to oral semaglutide treatment
Investigators will measure the change in glucose area under the curve (AUC) over 120 minutes of the MMTT, between the two visits, and compare this outcome by genotype at selected loci.
Time frame
15 days3
Baseline incretin level
Investigators will measure levels of GLP-1 during the length of the baseline MMTT (120 minutes) that takes place on Visit 1, and compare changes in the baseline levels by genotype at selected loci.
Time frame
120 minutes during Visit 1Sponsors and contacts
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Massachusetts General Hospital
Lead sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborator
Source ClinicalTrials.gov