bupropion + naltrexone + metformin

This is a combination of three pharmaceutical agents—bupropion, naltrexone, and metformin—sometimes considered for weight management or metabolic indications. Bupropion is an aminoketone antidepressant that acts as a weak inhibitor of the neuronal reuptake of norepinephrine and dopamine, stimulating pro-opiomelanocortin (POMC) neurons in the hypothalamus to reduce appetite. Naltrexone is an opioid receptor antagonist that blocks feedback inhibition on POMC neurons by β-endorphin, thereby enhancing the appetite-suppressing effect of bupropion. Metformin is a biguanide antihyperglycemic agent primarily used in type 2 diabetes; it improves insulin sensitivity and reduces hepatic glucose production. While bupropion/naltrexone (marketed as Contrave) is FDA-approved for chronic weight management in adults with obesity or overweight with comorbidities[1][2][6], metformin is not part of any approved fixed-dose combination with these agents but may be co-prescribed off-label for additional metabolic benefit.