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Metformin + ranolazine is a combination of two small molecule pharmaceuticals: metformin, a biguanide antihyperglycemic agent primarily used to treat type 2 diabetes, and ranolazine, an antianginal agent mainly used to treat chronic angina. Metformin acts by decreasing hepatic glucose production, decreasing intestinal absorption of glucose, and improving insulin sensitivity. Ranolazine inhibits the late phase of the inward sodium current in cardiac myocytes during cardiac repolarization, thereby reducing intracellular sodium and calcium accumulation, which improves myocardial relaxation and reduces angina symptoms. Notably, ranolazine can inhibit renal tubular transporters involved in metformin elimination, leading to higher metformin exposure—a clinically relevant drug-drug interaction. This combination may be used in patients with chronic angina and co-morbid type 2 diabetes, but co-administration increases metformin exposure, necessitating dosage modification and monitoring for adverse effects such as lactic acidosis, nausea, or dizziness[1][3][5].
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