Skip to main content
OpenTrials
Recruiting

NCT Number: NCT06003153

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

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.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Genetic Predisposition Diabetes Mellitus Diabetes Mellitus, Type 2 Disease Attributes Disease Susceptibility Endocrine System Diseases Genetic Predisposition to Disease Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Type 2 Diabetes

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location status: Recruiting

Location contact

Josephine Li, MD

PRINCIPAL_INVESTIGATOR

Varinderpal Kaur

CONTACT

[email protected]

6176435419

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Oral semaglutide

Drug

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)

Other

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 outcomes

  1. Insulin response to oral semaglutide treatment

    Time frame: 15 days

    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.

Secondary outcomes

  1. Fasting glucose response to oral semaglutide treatment

    Time frame: 15 days

    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.

  2. Cumulative glucose response to oral semaglutide treatment

    Time frame: 15 days

    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.

  3. Baseline incretin level

    Time frame: 120 minutes during Visit 1

    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.

Study contacts

Contact information is provided by the study sponsor or research team.

Josephine Li

CONTACT

[email protected]

617-643-4987

Varinderpal Kaur

CONTACT

[email protected]

6176435419

Sponsors and collaborators

Lead sponsor

Massachusetts General Hospital

Other

Collaborators

  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Registry information

Acronym: GLUCOSE-MGH

Important dates

Study start
2024
Primary completion
2027
Study completion
2027
First posted
Aug 21, 2023
Registry last updated
Jul 8, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.