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The problem emerged during polypharmacy

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Signs of overdose or toxic levels include intense agitation, a racing heartbeat, high blood pressure, hallucinations, seizures, and, in severe cases, unconsciousness or even death

The association between metformin and GDF15 was strengthened by data showing that metformin prevented weight gain in high fat fed mice, but not in mice lacking GDF15, or lacking its receptor, glial cell-derived neurotrophic factor family receptor alpha-like (GFRAL), or following treatment with a GRAL antagonist