Pharmaceuticals compositions comprising the 2S, 4R, ketoconazole enantiomer or its pharaceutically acceptable salts, hydrates, and solvates, that are substantially freee of the 2R, 4S ketoconazole enantiomer are useful to reduce cortisol synthese and for the treatment of type 2 diabetes, hyperglycemia, obesity, insulin resistance, dyslipidemia, hyperlipidemia, hypertension, Metabolic Syndrome, and other diseases and conditions, including but not limited to Cushing's Syndrome, depression, and glaucoma.