Recruiting

Oral Semaglutide

Sponsor:

Massachusetts General Hospital

Code:

NCT06003153

Conditions

Genetic Predisposition

Metabolic Diseases

Type 2 Diabetes

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Accepted

Interventions

oral semaglutide

Mixed Meal Tolerance Test (MMTT)

Study Details

Brief summary:

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.

Conditions

Genetic Predisposition

Metabolic Diseases

Type 2 Diabetes

Study ID

NCT06003153

Start date

Mar 12, 2024

Status verified date

Jul, 2026

Completion date

May 31, 2027

Anticipated

Primary completion date

May 31, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Accepted

Inclusion Criteria:

1. Males or non-pregnant females
2. Ages 18-65 (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

Study Design

Enrollment

125 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

other: GLUCOSE-MGH Study

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

Interventions

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.

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 measure

  • Insulin response to oral semaglutide treatment [ Time Frame: 15 days ]

Central Contacts and Locations

Central contacts

Varinderpal Kaur

6176435419vkaur@mgh.harvard.edu

Josephine Li

617-643-4987jli71@mgh.harvard.edu

Locations

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Contacts

Varinderpal Kaur

6176435419vkaur@mgh.harvard.edu

Principal Investigator:

Josephine Li, MD

More Information

Sponsor

Massachusetts General Hospital

Last update posted

Jul 8, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Massachusetts General Hospital on 2026-07-08.