A 54-year-old woman comes to the office for evaluation of elevated blood glucose. The patient was recently seen at an urgent care center, where she was found to have a nonfasting blood glucose level of 190 mg/dL. Medical history is insignificant, although she has not seen a physician for several years. She does not use tobacco or alcohol. BMI is 31.5 kg/m². Physical examination shows no abnormalities. Hemoglobin A1c is 8.5% and fasting plasma glucose level is 146 mg/dL. Recommendations for dietary modification and exercise are provided, and pharmacotherapy with metformin is planned. Which of the following laboratory tests should be obtained prior to starting this medication?

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11ec160b_3bae_df16_9249_b72b918ec2bc_MD0001_00 Metformin is the most commonly prescribed medication for type 2 diabetes mellitus. It reduces hepatic gluconeogenesis through multiple mechanisms, including inhibition of glycerophosphate dehydrogenase and complex I (the first enzymes in the electron transport chain) and upregulation of AMP-activated protein kinase. These mechanisms reduce the availability of substrates for gluconeogenesis (eg, dihydroxyacetone phosphate, pyruvate, fatty acids) and increase peripheral glucose uptake and utilization. Metformin does not increase endogenous insulin secretion and is therefore less likely to cause hypoglycemia than sulfonylureas or insulin. The inhibition of gluconeogenic enzymes by metformin results in buildup of substrate molecules that are released into the plasma; decreased formation of pyruvate results in excess buildup of its precursor, lactate, which increases the risk of lactic acidosis. Although rare, the risk is increased in those with significant renal dysfunction or other disorders causing decreased lactate clearance (eg, hepatic impairment, congestive heart failure). For this reason, the glomerular filtration rate should be estimated using serum creatinine measurement prior to initiation of metformin therapy. (Choice A) Metformin can cause vitamin B₁₂ deficiency, likely due to decreased intestinal absorption. However, this is a chronic effect seen after long-term use, and preprescription testing is not needed. (Choice B) The oral glucose tolerance test can be used for initial diagnosis of diabetes or primarily gestational diabetes. This patient's diagnosis has been confirmed with the elevated fasting glucose and hemoglobin A1c; additional diagnostic testing is not necessary. (Choice C) Plasma lactate levels are used to confirm acute lactic acidosis; measurement of a baseline level is not necessary. (Choice E) Monitoring serum potassium is not necessary with metformin use. Serum potassium is routinely monitored with diuretics (especially loop diuretics), spironolactone, ACE inhibitors, and angiotensin II receptor blockers. (Choice F) Thyroid function tests are not required for any antidiabetic medications, including metformin. They are routinely performed in patients taking lithium and amiodarone. Educational objective: Metformin inhibits hepatic gluconeogenesis and increases peripheral glucose utilization. Lactic acidosis is a rare complication of metformin therapy, but its risk is increased in patients with underlying renal insufficiency. __________ References: Metformin-associated lactic acidosis: predisposing factors and outcome. (http://www.ncbi.nlm.nih.gov/pubmed/25827460) Metformin in patients with type 2 diabetes and kidney disease: a systematic review. (http://www.ncbi.nlm.nih.gov/pubmed/25536258)

A 54-Year-Old Woman Comes to the Office for Evaluation of Elevated