Title: Therapeutic Targets in African-American Youth With Type 2 Diabetes

NCT02960659 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 17001317-DK-0013
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Background: The pill metformin treats diabetes. But it does not work for all youth, especially African-Americans. The injectable Liraglutide treats type 2 diabetes in adults. Researchers want to understand how these drugs work and if they decrease excess sugar made by the liver in youth with type 2 diabetes. Objective: To test if using liraglutide and metformin are better than just metformin for decreasing excess sugar produced by the liver in African-American youth with type 2 diabetes. Eligibility: African-Americans ages 12-25 with type 2 diabetes Design: Visit 1: Participants will be screened with medical history, physical exam, and blood and urine tests. Participants will stop taking diabetes medicines for 1 week. They will learn how to check blood sugars at home twice a day. Visit 2: Overnight at the clinic. Participants will have: Vital signs taken. Pregnancy test. A thin plastic tube (IV catheter) be inserted in each forearm by needle. Blood drawn several times after drinking a sweet drink. X-ray of total body fat. Urine and stool collected. Breath tests while wearing a clear hood for up to 45 minutes. For several hours, participants can have only water. At 4 a.m. they will get sugar and fat with nonradioactive isotopes in one IV. Blood will be collected. Every 30 minutes from 9 a.m. to 2 p.m., they will drink small amounts of a shake and have blood drawn. Participants will be randomly assigned to take either both study drugs daily or just metformin daily. Visits 3-4: Participants will bring their blood sugar records and have blood tests. Visit 5, after 3 months: Repeat of visit 2....

Conditions

Type 2 Diabetes

Keywords

Diabetes; Metformin; Glucose

Outcome Measures

Primary Outcomes (1)

• Change in Absolute Gluconeogenesis From Baseline to 12 Weeks

  Gluconeogenesis is measured using stable isotope tracers and is reported as mg/kg lean body mass (LBM) per minute

  Baseline to 12 weeks

Secondary Outcomes (8)

• Change in Glucose Production Rate From Baseline to 12 Weeks

  Baseline to 12 weeks

• Change in GIP AUC During OGTT and Meal Absorption

  Baseline to 12 weeks

• Change in GLP-1 Area Under the Curve Concentrations (AUC) During OGTT and Meal Absorption

  Baseline to 12 weeks

• Change in Whole Body Insulin Sensitivity From Baseline to 12 Weeks

  Baseline to 12 weeks

• Change in Hepatic Insulin Sensitivity Index From Baseline to 12 Weeks

  Baseline to 12 weeks

Study Arms (2)

Metformin

ACTIVE COMPARATOR

Standard release metformin (500 mg tablets) was initiated and titrated to maximum dose of metformin 1000 mg twice daily over 3 weeks and continued for 12 weeks

Drug: Metformin

Metformin and liraglutide

EXPERIMENTAL

Standard release metformin (500 mg tablets) and liraglutide (0.6mg) were initiated and titrated to maximum dose of metformin 1000 mg twice daily, and liraglutide 1.8 mg daily over 3 weeks and continued for 12 weeks

Drug: Liraglutide; Drug: Metformin

Interventions

Liraglutide DRUG

Liraglutide (6mg/ml, 3ml ) solution for subcutaneous injection, pre-filled, multi-dose pen that delivers doses of 0.6mg, 1.2mg or 1.8mg.

Metformin and liraglutide

Metformin DRUG

Metformin 500mg oral tablet

Metformin; Metformin and liraglutide

Eligibility Criteria

• Age: 12 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Youth must self-identify as African-American and identify both parents as African-American
• Age 12-25 years
• Pubertal or post-pubertal: Girls Tanner stage IV-V breast; Boys Testicular volume 11-25cc
• Diagnosis of type 2 diabetes of less than or equal to 5 years duration, as per American Diabetes Association Criteria
• Hemoglobin A1C \<9% at study initiation
• Negative to mild ketonuria without acidosis (negative or 1+ ketones on urinalysis)
• Negative test for diabetes-related autoantibodies (glutamic acid decarboxylase 65 and tyrosine phosphatase-related islet antigen 2 (IA-2))
• Willing and able to take daily medications and check blood glucose levels at least twice per day or wear a continuous glucose monitoring device (CGM).

You may not qualify if:

• Pregnancy or breastfeeding
• Allergy to study medications
• Allergy to milk protein
• Chronic insulin therapy
• Treatment with other medications which are known to affect the parameters under study (for example sodium glucose transporter 2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 (DPP-IV) inhibitors, non-selective beta blockers).
• Metabolic derangement such as metabolic acidosis, severe hyperglycemia (fasting blood glucose greater than or equal to 200mg/dL), and/or liver enzymes \> three times the upper limit of normal.
• Personal or family history of medullary thyroid cancer or Multiple Endocrine Neoplasia syndrome type 2
• Any other condition that, in the opinion of the investigators, will increase risk to the subject, or impede the accurate collection of study-related data.
• Body weight greater than or equal to 450 lbs
• Body weight less than or equal to 58kg
• Serum triglyceride concentrations greater than or equal to 500mg/dl
• Hemoglobin concentration \<10g/dL

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead
• Children's National Research Institute: collaborator

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Glaros SB, Mishra SP, Jain S, Davis FS, Gabel SA, Mueller GA, Jarmusch AK, Mabundo L, Courville AB, Walter MF, Walter PJ, Overdahl KE, Yadav H, Chung ST. Systemic and gut microbiome changes with metformin and liraglutide in youth-onset type 2 diabetes: the MIGHTY study. Gut Microbes. 2025 Dec;17(1):2558071. doi: 10.1080/19490976.2025.2558071. Epub 2025 Sep 29.

  PMID: 41020378 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Interventions

Liraglutide; Metformin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Dr. Stephanie Chung
• Organization: NIDDK

stephanie.chung@nih.gov

301-402-2122

Study Officials

• Stephanie T Chung, MBBS

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2016
• First Posted: November 10, 2016
• Study Start: May 9, 2017
• Primary Completion: May 20, 2022
• Study Completion: May 20, 2022
• Last Updated: August 1, 2023
• Results First Posted: August 1, 2023

Record last verified: 2023-04-12

Data Sharing

• IPD Sharing: Will share

Locations

US (1)