Study of Clinical Response to Acute Metformin By Leveraging Evaluations During a Mixed Meal Tolerance Test for Exploring Glycemia and GeneticS

NCT02087826 | Active Not Recruiting DMC

• 1 other identifier: 2014P000255
• Study Type: interventional
• Target: 1,017
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to examine whether specific genes (e.g. SLC16A11) affect how human beings respond to food and a medication that is commonly used to treat type 2 diabetes. The food the investigators will be studying is specially prepared to contain protein, carbohydrate, and fat. The drug the investigators are studying is metformin. The investigators hypothesize that physiological responses to the meal and to the medication will differ between carriers and non-carriers of genes associated with type 2 diabetes.

Conditions

Genetics; Metabolism; Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Response to the Mixed Meal Tolerance Test

  Primary endpoint point: 2 hr glucose after the MMTT Secondary endpoints: 2 hr insulin after the MMTT, change in glucose, insulin, and amino acid and lipid metabolites from baseline to 60 and 120 minutes after the MMTT; change in GLP-1 concentrations from baseline to 5,10, 15, 30, 60, and 120 minutes after the MMTT; and glucose, insulin, and GLP-1 AUC over 120 minutes

  2 hours after the meal

Secondary Outcomes (1)

• Response to Metformin

  Day 8 of the study

Other Outcomes (1)

• Response to a Mixed Meal Tolerance Test after Metformin

  2 hours after the meal

Study Arms (2)

Carriers of the SLC16A11 risk allele

ACTIVE COMPARATOR

Day 1: Mixed Meal Tolerance Test Day 3-7: 500mg metformin, twice daily Day 8: Mixed Meal Tolerance Test in presence of Metformin

Other: Mixed Meal Tolerance Test; Drug: Metformin

Non-carriers of the SLC16A11 risk allele

PLACEBO COMPARATOR

Day 1: Mixed Meal Tolerance Test Day 3-7: 500mg metformin, twice daily Day 8: Mixed Meal Tolerance Test in presence of Metformin

Other: Mixed Meal Tolerance Test; Drug: Metformin

Interventions

Mixed Meal Tolerance Test OTHER

The meal will provide a standard amount of total calories, protein, fat, and carbohydrate to each participant at both study visits. Pre-packaged and prepared food, weighed to the nearest gram, will be used.

Carriers of the SLC16A11 risk allele; Non-carriers of the SLC16A11 risk allele

Metformin DRUG

Metformin will be administered during this study. This medication is safely prescribed at a maximum dose of 1000 mg twice daily for the treatment or prevention of type 2 diabetes, as well as for other metabolic conditions. To minimize potential side effects of metformin (e.g., GI upset), participants will take ½ the maximum dose of this medication (500 mg twice daily) and for only 5 days. Participants will be informed of the potential side effects of metformin. They will be asked to contact study staff and discontinue the medication if symptoms are very uncomfortable.

Also known as: Glucophage, Glumetza, Glucophage XR, Fortamet

Carriers of the SLC16A11 risk allele; Non-carriers of the SLC16A11 risk allele

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult males or non-pregnant females
• Age 18-79
• Able and willing to give consent relevant to genetic investigation

You may not qualify if:

• Women who are pregnant, nursing, or at risk of becoming pregnant
• Currently taking any medications used for the treatment of diabetes
• History of liver disease and/or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than 3 times upper limit of normal (ULN)
• Estimated glomerular filtration rate (eGFR) \< 60 ml/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation
• Currently taking or intending to take during the study duration any medication known to affect glycemic parameters, such as glucocorticoids, growth hormone, or fluoroquinolones
• Contraindications to safe use of metformin, including planned radiologic or angiographic study requiring contrast within one week of the study completion
• Planned changes to any prescribed medications, specifically diuretics, during study enrollment
• Participation in any other interventional study during the study duration
• Conditions causing intestinal malabsorption, including celiac disease or a history of intestinal or gastric bypass surgery
• Dietary restrictions that would prevent consumption of a MMTT
• Objection or inability to take metformin

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Instituto Carlos Slim de la Salud: collaborator
• Broad Institute of MIT and Harvard: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Laura N Brenner, MD

  Massachusetts General Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Instructor in Medicine

Study Record Dates

• First Submitted: March 12, 2014
• First Posted: March 14, 2014
• Study Start: April 1, 2014
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 15, 2026

Record last verified: 2026-01

Locations

US (1)