Semaglutide Effects in Obese Youth With Prediabetes/New Onset Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease

Inclusion Criteria20

• 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.
• 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:
• History of major depressive disorder within 2 years before screening
• Diagnosis of other severe psychiatric disorders (e.g., schizophrenia, bipolar disorder)
• A Patient Health Questionnaire-9 (PHQ-9) score of ≥15 at screening
• A lifetime history of suicidal attempt
• Suicidal behavior within 30 days before screening
• Suicidal ideation corresponding to type 4 or 5 based on the Columbia-Suicide Severity
• Rating Scale (C-SSRS) within the past 30 days before screening
• Participants with confirmed diagnosis of bulimia nervosa disorder