Glycemic Effect of Diazoxide in NAFLD

Study Summary

The goal of this clinical trial is to compare a two-week course of diazoxide (at two different doses) and placebo in people with overweight/obesity and insulin resistance (IR) with, or at high risk for, non-alcoholic fatty liver disease (NAFLD). The main questions it aims to answer are how mitigation of compensatory hyperinsulinemia with diazoxide affects parameters of glucose and lipid metabolism (how people with IR and NAFLD respond to lowering high insulin levels so that the investigators can see what happens to how the liver handles fat and sugar). Participants will: * Take 27 doses of diazoxide (at 1 mg per kg of body weight per dose \[mpk\] or 2 mpk) or of placebo, over 14 days * Take 32 doses of heavy (deuterated) water (50 mL each) over 14 days * Have blood drawn and saliva collected after an overnight fast on four mornings over the two-week study period * Consume their total calculated daily caloric needs as divided into three meals per day * Wear a continuous glucose monitor for the two-week study period Researchers will compare fasting blood tests at intervals during the study period in participants randomized (like the flip of a coin) to diazoxide 1 mpk, diazoxide 2 mpk, or placebo, to see how the drug treatment affects plasma glucose, serum insulin, and serum lipid parameters (triglycerides, free fatty acids, and apolipoprotein B). They will also consume heavy (deuterated) water to assess de novo lipogenesis (building of new fatty acids by the liver).

Primary Outcome

Measurement of fasting plasma glucose levels during treatment with diazoxide 1 mpk vs 2 mpk vs placebo (units: mg/dL).

Interventions

• DRUG Placebo
• DEVICE FreeStyle Libre Pro
• DRUG Diazoxide oral suspension, 1 mg per kg per dose
• DRUG Diazoxide oral suspension, 2 mg per kg per dose
• DRUG Deuterated water (2H2O/D2O)