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

NCT06003153 | Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: 2023P001852K23DK131345
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 1

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

Outcome Measures

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.

  15 days

Secondary Outcomes (3)

• Fasting glucose response to oral semaglutide treatment

  15 days

• Cumulative glucose response to oral semaglutide treatment

  15 days

• Baseline incretin level

  120 minutes during Visit 1

Study Arms (1)

GLUCOSE-MGH Study

OTHER

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

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

Interventions

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.

GLUCOSE-MGH Study

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.

GLUCOSE-MGH Study

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males or non-pregnant females
• Ages 18-50 (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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

MeSH Terms

Conditions

Genetic Predisposition to Disease; Metabolic Diseases; Diabetes Mellitus, Type 2

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Disease Susceptibility; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Endocrine System Diseases

Study Officials

• Josephine Li, MD

  MGH

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Varinderpal Kaur

CONTACT

6176435419; vkaur@mgh.harvard.edu

Josephine Li

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: August 9, 2023
• First Posted: August 21, 2023
• Study Start: March 12, 2024
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027
• Last Updated: May 1, 2025

Record last verified: 2025-04

Locations

US (1)