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.

NCT Number	NCT06003153
Lead Sponsor	Massachusetts General Hospital Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Conditions	Genetic Predisposition, Metabolic Diseases, Type 2 Diabetes
Enrollment	125 participants
Start Date	2024-03-12
Primary Completion	2027-05-31 (estimated)
Study Completion	2027-05-31 (estimated)
Updated on ClinicalTrials.gov	2026-07-08