A 52-year-old woman comes to the office for follow-up of type 2 diabetes mellitus. The patient was diagnosed with diabetes 6 months ago and initiated intensive lifestyle modification with increased exercise and a calorie-restricted diet; since that time, she has felt better subjectively but has lost only 2 kg (4.4 lb) . Vital signs are normal. BMI is 35 kg/m². Fasting glucose is 155 mg/dL and hemoglobin A1c is 8.0%. Serum renal and liver function markers are normal. After discussion with the patient, metformin therapy is initiated. Which of the following physiologic changes are most likely to result as a direct effect of this medication?

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11ec160b_3bb4_f9a2_9249_8bf59d2f0b11_MD0001_00 This patient has uncontrolled type 2 diabetes mellitus and is appropriately given metformin, which is the preferred first-line medication for most patients. Metformin has a number of important metabolic effects: Circulating levels of endogenous insulin are unchanged or slightly decreased by metformin; therefore, metformin carries low risk of hypoglycemia. In addition, it reduces caloric intake due to decreased appetite and decreased absorption of glucose, leading to modest weight loss in most patients. (Choice A) Sulfonylureas (eg, glyburide, glimepiride) stimulate beta cell insulin release, leading to decreased glycogenolysis and gluconeogenesis and increased peripheral uptake of glucose; the higher circulating insulin levels also confer an increased risk of hypoglycemia and weight gain. Educational objective: Metformin reduces hepatic gluconeogenesis and release of glucose into circulation; increases peripheral glucose uptake and utilization; and reduces circulating lipid levels. Circulating insulin levels are unchanged or slightly decreased; therefore, metformin carries low risk of hypoglycemia. In addition, metformin reduces caloric intake due to decreased appetite and decreased absorption of glucose, leading to modest weight loss.

A 52-Year-Old Woman Comes to the Office for Follow-Up of Type