Effect of Insulin Lowering on Lipogenesis

Inclusion Criteria: * Adults aged 18-65 years * Body mass index of 30-45 kg/m2 * Able to understand written and spoken English and/or Spanish * Able to have pre-randomization screening labs drawn and study protocol initiated within 60 days of eligibility determination * Presence of uncomplicated metabolic dysfunction-associated steatotic liver disease (MASLD) by vibration-controlled transient elastography (VCTE) * Steatosis score of S1-S3 * Fibrosis score of F0-F2 (Note that if VCTE result is available from within past 6 months, then do not have to repeat VCTE for study purposes) * Evidence of insulin resistance, represented by any or all of the following criteria: * Meeting either of the American Diabetes Association's definitions for prediabetes or impaired fasting glucose (IFG) on screening labs: * Prediabetes: Hemoglobin A1c 5.7-6.4% * IFG: plasma glucose of 100-125 mg dL-1 after ≥ 8-h fast * Homeostasis Model of Insulin Resistance (HOMA-IR) score ≥ 2.73 * Fasting hyperinsulinemia (fasting insulin level ≥ 13 μU/mL) on screening labs * Written informed consent (in English or Spanish) and any locally required authorization (e.g., Health Insurance Portability and Accountability Act) obtained from the participant prior to performing any protocol-related procedures, including screening evaluations. Exclusion Criteria: * Unable to provide informed consent in English or Spanish * Concerns arising at screening visit (any of the following): * Documented weight loss of ≥ 5.0% of baseline within the previous 3 months * Abnormal blood pressure (including on treatment, if prescribed) * Systolic blood pressure (SBP) \< 90 mm Hg or \> 160 mm Hg, and/or * Diastolic blood pressure (DBP) \< 60 mm Hg or \> 100 mm Hg * Resting heart rate \< 55 bpm or ≥ 110 bpm * Abnormal screening electrocardiogram (or if on file, performed within previous 90 days) * Laboratory evidence of diabetes mellitus: * Hemoglobin A1c ≥ 6.5%, and/or * Fasting plasma glucose ≥ 126 mg/dL * Positive qualitative serum β-human chorionic gonadotropin (β-hCG, i.e., pregnancy test) in women of childbearing potential * Liver function abnormalities: transaminases (aspartate aminotransferase or alanine aminotransferase) \> 3.0 x the upper limit of normal, and/or total bilirubin \> 1.25 x the upper limit of normal * Abnormal screening fasting triglycerides \> 500 mg/dL * Abnormal screening serum electrolytes that are considered clinically significant according to the clinical judgment of the PI * Creatinine equating to estimated glomerular filtration rate \< 60 mL/min/1.73 m2 * Abnormal screening blood counts (any of the following): * Hemoglobin \< 10 g/dL * White blood cell count below the lower limit of normal for sex * Platelet count below the lower limit of normal for sex * Uric acid level above the upper limit of normal * Reproductive concerns * Women currently pregnant (tested by serum and/or urine β-hCG) * Women currently breastfeeding * Concerns related to glucose metabolism * History of having met any of the American Diabetes Association's definitions of diabetes mellitus (i.e., overt diabetes): * Hemoglobin A1c ≥ 6.5% * Plasma glucose ≥ 126 mg/dL after 8-h fast * Plasma glucose of ≥ 200 mg/dL at 2 h after ingestion of a 75-g glucose load * Random plasma glucose ≥ 200 mg/dL associated with typical hyperglycemic symptoms, diabetic ketoacidosis, or hyperglycemic-hyperosmolar state * History of gestational diabetes mellitus within the previous 5 years * Use of antidiabetic medications except metformin within the 90 days prior to screening * Clinical concern for absolute insulin deficiency (e.g., type 1 diabetes, pancreatic disease) * Concerns related to lipid metabolism * Known diagnoses of familial hypercholesterolemia, familial combined hyperlipidemia, or familial hyperchylomicronemia * Use of fibrates, prescription-strength omega-3 fatty acids, or high-dose niacin within the 90 days prior to screening: * Known, documented history (i.e., not to be newly screened/tested for study purposes), at the time of screening, of any of the following medical conditions: * Pancreatic pathology, including but not limited to neoplasia, pancreatitis, pancreatectomy * Cardiovascular disease (N.B. uncomplicated hypertension is not exclusionary) * Atherosclerotic cardiovascular disease: stable or unstable angina, myocardial infarction, ischaemic or hemorrhagic stroke, or transient ischaemic attack, peripheral arterial disease (claudication), use of dual antiplatelet therapy (aspirin + P2Y12 inhibitor), history of percutaneous coronary intervention * Heart rhythm abnormalities * Congestive heart failure of any New York Heart Association class * Symptomatic valvular heart disease (e.g., aortic stenosis) * Pulmonary hypertension * Chronic kidney disease, Stage 3 or higher (estimated glomerular filtration rate \< 60 mL/min/ 1.73 m2), of any cause * Chronic liver disease other than uncomplicated MASLD, including but not limited to: * Advanced liver fibrosis, as determined by non-invasive testing, including fibrosis scores of F3-F4 on VCTE * Cirrhosis of any etiology * Autoimmune hepatitis or other rheumatologic disorder affecting the liver * Biliopathy (e.g., progressive sclerosing cholangitis, primary biliary cholangitis) * Chronic liver infection (e.g., viral hepatitis, parasitic infestation) * Hepatocellular carcinoma * Infiltrative disorders (e.g., sarcoidosis, hemochromatosis, Wilson disease) * Gout * Chronic infection with hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) * Malabsorptive conditions * Active seizure disorder (including controlled with antiepileptic drugs) * Psychiatric diseases that are or have been decompensated within 1 year of screening, and/or require use of antipsychotic drugs associated with significant weight ga