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Five placebo-controlled add-on combination therapy studies were also conducted one with metformin; one with pioglitazone; one with metformin and rosiglitazone; one with glimepiride with or without metformin ; and one with insulin with or without metformin .

Metformin inhibits tumorigenesis through multiple mechanisms including the induction of cancer cell death in conditions, when glucose is limited and through inhibition of mitochondrial ros-dependent signaling pathways that promote tumorigenesis i.

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There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with metformin or any other antidiabetic drug.

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there was, however, an increased incidence of benign stromal uterine polyps in female rats treated with 900 mg kg day of metformin alone.