exemestane + metformin + rosiglitazone

This is a combination of three small molecule drugs—exemestane, metformin, and rosiglitazone—investigated for use in non-diabetic overweight and obese postmenopausal women with hormone receptor-positive metastatic breast cancer. Exemestane is a steroidal aromatase inhibitor that reduces estrogen production, thereby inhibiting the growth of estrogen-dependent breast cancer cells. Metformin is an oral biguanide antihyperglycemic agent that improves insulin sensitivity and decreases hepatic glucose production. Rosiglitazone is a thiazolidinedione class drug that acts as an agonist at peroxisome proliferator-activated receptor gamma (PPARγ), enhancing tissue sensitivity to insulin. The rationale for this combination targets both endocrine resistance (via exemestane) and metabolic dysfunction/insulin resistance (via metformin and rosiglitazone), which are implicated in poor prognosis among obese women with breast cancer[1][2][9]. This specific triple-drug regimen has been studied in phase I clinical trials to assess safety, tolerability, and pharmacokinetics[1][2].