Semaglutide Effects in Obese Youth With Prediabetes/New Onset Type 2 Diabetes and Metabolic Dysfunction-Associated Steatotic Liver Disease

NCT05067621 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 20000311812R01DK111038-06A1
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to understand the role of GLP-1 in the pathogenesis of T2D in youth and explore their potential salutary effects and ability to delay the progressive loss of ß-cell function and reduce hepatic steatosis in youth with prediabetes/new onset T2D and NAFLD.

Conditions

Type 2 Diabetes Mellitus; Impaired Glucose Tolerance; Non-Alcoholic Fatty Liver Disease; Obesity, Childhood

Keywords

Prediabetes; NAFLD; Impaired Glucose Tolerance; Semaglutide

Outcome Measures

Primary Outcomes (2)

• Change in Oral Disposition Index (oDI)

  The oDI value is the product of total responsivity index and insulin sensitivity. The change in oDI from baseline to 6M on treatment is calculated as the difference between 6M oDI value and baseline oDI value. The oDI measures the ability of beta-cell to respond to a glucose stimulus.

  Baseline and 6 months

• Change in Protein Density Fat Fraction (PDFF)

  The change in PDFF from baseline to 6M on treatment is calculated as the difference between 6M PDFF value and Baseline PDFF. It provides an accurate, non-invasive, reproducible, quantitative, and precise estimation of liver fat content. The expected changes in MRI-PDFF from baseline to 6M is ≥ 5.8% reduction compared to the placebo group.

  Baseline and 6 months

Secondary Outcomes (27)

• Change in Oral glucose tolerance test (OGTT) derived biomarkers: oDI

  Baseline and 9 months

• Change in OGTT derived biomarkers: fasting insulin

  Baseline and 6 months

• Change in OGTT derived biomarkers: fasting insulin

  Baseline and 9 months

• Change in OGTT derived biomarkers: c-peptide

  Baseline and 6 months

• Change in OGTT derived biomarkers: c-peptide

  Baseline and 9 months

Other Outcomes (2)

• Changes in liver fibrosis

  6 months

• Changes in liver fibrosis

  9 months

Study Arms (2)

Receive treatment

EXPERIMENTAL

Semaglutide (Wegovy) pen is a subcutaneous injection

Drug: Semaglutide Pen Injector

Placebo

PLACEBO COMPARATOR

The placebo pen is almost exactly the same as the Wegovy subcutaneous injection except it does not contain the active ingredient, Semaglutide.

Drug: Placebo

Interventions

Semaglutide Pen Injector DRUG

Semaglutide (Wegovy) pen is a subcutaneous injection that contains 2.4mg/0.75mL of active ingredient. The injection pen can deliver doses of 0.24mg, 0.5mg, 1.0mg, 1.7mg, and 2.4mg.

Also known as: Wegovy

Receive treatment

Placebo DRUG

Injection pen contains excipients.

Placebo

Eligibility Criteria

• Age: 10 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Subjects diagnosed with Pre-impaired glucose tolerance (pre-IGT) (2h glucose ≥ 130 mg/dl to ≤ 200 mg/dl post-OGTT) OR impaired glucose tolerance (2h glucose ≥140 to \<200 mg/dl post-OGTT OR HbA1c ≥5.7% to \<6.5%), OR new-onset T2D (≤24 months duration, 2h glucose \>200 and HbA1c \>6.5% to10%) treated with stable metformin dose (stable metformin dose is defined as at least 1000 mg daily or the maximum tolerated dose for 12 months or less)
• PDFF of ≥ 8%
• Male or female, aged 10 to \<21 years at the day of randomization, in puberty (pubertal stage will be assessed by pediatric Endocrinologists Dr. Samuels and Dr. Hu) (girls and boys: Tanner stage II-IV); girls who begin menstruating must have a negative pregnancy test during the study
• Weight ≥ 54kg
• BMI ≥ 85% but ≤ 40 kg/m2
• Good general health (normal kidney function, amylase, and lipase levels)
• Informed consent from a legally acceptable representative (LAR) and child assent from the subject obtained before any trial-related activities (trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial)
• Ability and willingness to adhere to the protocol including self-measurement of plasma glucose according to the protocol.

You may not qualify if:

• Known or suspected hypersensitivity to trial product(s) or related products.
• Receipt of any investigational medicinal product within 30 days before screening.
• Prepubertal participants (Tanner stage 1)
• Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using highly effective contraceptive methods.
• Having a diagnosis of:
• Type 1 diabetes o Maturity onset diabetes of the young (MODY) o History or presence of Pancreatitis (acute or chronic) o Presence of endocrinopathies (e.g., Cushing syndrome) o Cardiac, renal or pulmonary or other chronic illness o Known history of heart disease (including history of clinically significant arrhythmias or conduction delays on ECG, or new clinically significant arrhythmias or conduction delays on ECG identified at visit 1) o Family or personal history of MEN type 2 or medullary thyroid carcinoma (family is defined as a first-degree relative)o Any other disorder which, in the opinion of the investigator, might jeopardize subject's safety or compliance with the protocol
• Any laboratory safety parameter at screening outside the below extended laboratory ranges: o Baseline creatinine \>1.0mg o Hypertriglyceridemia)(\>500 mg/dl)
• Calcitonin equal or above 50 ng/L at screening o Body Mass Index (BMI) ≤ 25.0 at the screening visit o ALT ≥5 times the upper normal limit (UNL) o Creatinine \>UNL for age in children unless renal function is proven normal by further assessments at the discretion of the investigator
• Known hypoglycemic unawareness.
• Recurrent severe hypoglycemic episodes within the last year as judged by the investigator.
• Uncontrolled hypertension treated or untreated \>99th percentile for age and gender in children and adolescents.
• Taking medication, based on the investigator's judgement, that may cause significant weight gain or loss (e.g., antipsychotic, steroid, anti-obesity medication).
• Presence or history of malignant neoplasm within 5 years prior to the day of screening.Basal and squamous cell skin cancer and any carcinoma in-situ is allowed.
• Positive insulinoma associated-protein 2 (IA-2) antibodies or anti-glutamic acid decarboxylase (anti-GAD) antibodies.
• Mental health:

Sponsors & Collaborators

• Yale University: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Pediatric Diabetes Center

New Haven, Connecticut, 06511, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Glucose Intolerance; Non-alcoholic Fatty Liver Disease; Pediatric Obesity; Prediabetic State

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperglycemia; Fatty Liver; Liver Diseases; Digestive System Diseases; Obesity; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Sonia Caprio, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Yale Investigational Drug Services Pharmacy will handle the masking of drug and placebo pens.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Participants will undergo baseline tests at the beginning of the study and will be randomized to receive experimental drug or placebo. Dose escalation will be achieved within 16 weeks to reach up to 2.4mg of Semaglutide, weekly, which they will be on for 6 months. All tests will be repeated after 6 months of treatment followed by a wash-out period of 3 months, after which the same tests will be repeated.

Study Record Dates

• First Submitted: September 21, 2021
• First Posted: October 5, 2021
• Study Start: July 17, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)