Current treatment guidelines recommend initiating metformin as first line pharmacotherapy unless a contraindication or intolerability exists.
Metformin consistently reduces A1C levels by 1.5% to 2.0% and FPG levels by 60 to 80 mg/dL (3.3 to 4.4 mmol/L) in drug naive patients with A1C values of approximately 9%.
Metformin does not cause weight gain, and may actually lead to a modest (2-3 kg) weight loss.
Since metformin does not directly increase insulin secretion from the pancreas, it has a low risk of hypoglycemia.
Metformin frequently causes GI side effects, including diarrhea, abdominal discomfort, and/or stomach upset. These side effects are usually dose-dependent, transient, mild in nature, and can be minimized with slow dose titration.
Patients should take metformin with or immediately after meals. When initiating therapy, it is important to use a low dose, typically 500 mg given with the largest meal, to minimize GI adverse effects. The dose is then increased in 500 mg increments over several weeks.
Approximately 5% to 10% of patients cannot tolerate metformin despite the slow dose titration.
Extended-release metformin may lessen some of the GI side effects, but a recent head to head comparison of immediate-release versus extended-release metformin found no significant differences in rates of GI adverse effects.
Metformin may cause a metallic taste, due to metformin in salivary secretions and may lower vitamin B12 concentrations.
Rare cases of lactic acidosis have been reported with metformin, usually in the setting of severe illness or acute kidney injury. The risk appears to be exceedingly small but may increase in patients with moderate to severe renal insufficiency or tissue hypo-perfusion states such as acute congestive heart failure, excessive alcohol intake, and hepatic impairment.
Metformin can be used in combination with any other antihyperglycemic therapy and is often continued when insulin therapy is initiated.
The target dose for metformin is 1,000 mg twice daily or 2,000 mg daily if the extended-release product is used. The minimal effective dose of metformin is 1,000 mg/day.
Approximately 80% of the glycemic lowering effect may be seen at 1,500 mg daily.
Metformin is renally excreted and accumulates in patients with renal insufficiency; therefore, metformin is contraindicated in patients with an eGFR < 30 mL/min/1.73 m2 and should be used with caution in patients with milder renal insufficiency. Initiation of metformin is not recommended in patients with an eGFR 30-45 mL/min/1.73 m2 but can be continued with increased renal function monitoring; a dose reduction of 50% of maximal dose may be warranted.
Due to the risk of acute renal failure when IV contrast dye is used during imaging procedures, metformin therapy should be withheld starting the day of the procedure and resumed 2 to 3 days later, if normal renal function has been documented. It need not be withheld for days prior to the procedure.
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Resource Person: Lobna Adi