What is the main risk associated with Metformin in patients with a GFR less than 45 mL/min/1.73 m²?

Lactic acidosis is a significant risk associated with the use of Metformin in patients who have a glomerular filtration rate (GFR) of less than 45 mL/min/1.73 m². Metformin is primarily eliminated by the kidneys, and impaired renal function can lead to an accumulation of the drug in the body. When Metformin levels rise excessively, there is an increased risk of lactic acidosis due to the drug's mechanism of action, which can contribute to lactate production and interfere with lactate clearance.

Patients with decreased renal function may have difficulty excreting lactate, further exacerbating the situation. This condition is serious and can be life-threatening, with symptoms that include hyperventilation, abdominal pain, and altered mental status. Due to these risks, it is crucial for healthcare providers to monitor kidney function regularly and to be cautious with Metformin prescription in these populations, often recommending alternative treatments when GFR falls below a certain threshold.

In contrast, while worsening renal function, hypokalemia, and hypocalcemia can be concerns in various clinical scenarios, they are not the primary risks directly associated with the use of Metformin at reduced GFR levels.