GLUCOSE-MGH: Genetic Links Understood Through Challenge With Oral Semaglutide Exposure at MGH

Mass General Brigham

Status and phase: Enrolling; Phase 4

Conditions: Metabolic Diseases; Genetic Predisposition; Type 2 Diabetes

Treatments: Drug: oral semaglutide; Other: Mixed Meal Tolerance Test (MMTT)

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06003153

K23DK131345 (U.S. NIH Grant/Contract)

2023P001852

Details and patient eligibility

About

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.

Full 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.

Enrollment: 125 estimated patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Males or non-pregnant females
2. Ages 18-50 (inclusive)
3. Able/willing to give consent
4. 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

1. Currently taking medications or intending to take medications for diabetes
2. Currently taking medications or intending to take medications that affect glycemic parameters, such as glucocorticoids, growth hormone, or fluoroquinolones
3. Personal history of intestinal malabsorption, bariatric surgery, celiac disease, gallbladder disease, or pancreatitis
4. Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2
5. Estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 per the Modification of Diet in Renal Disease equation
6. History of cirrhosis and/or aspartate aminotransferase or alanine aminotransferase more than 3x upper limit of normal
7. Dietary restrictions preventing consumption of a MMTT
8. Women who are pregnant, nursing, or at risk of becoming pregnant
9. Participation in other interventional studies during the current study

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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125 participants in 1 patient group

GLUCOSE-MGH Study

Other group

Description:

Day 1: Mixed meal tolerance test Day 3-15: 7 mg oral semaglutide, once daily Day 16: 1 dose of 7 mg oral semaglutide, Mixed meal tolerance test in the presence of semaglutide

Treatment:

Other: Mixed Meal Tolerance Test (MMTT)

Drug: oral semaglutide