A 45-year-old woman comes to the office for follow-up of type 2 diabetes mellitus. The patient was diagnosed with diabetes 3 years ago after developing polyuria, polydipsia, and recurrent vulvovaginal candidiasis. She initially tried lifestyle changes but had no significant glycemic improvement and was started on metformin. The patient is adherent with her therapy and consumes a low-carbohydrate diet. Family history is significant for an osteoporotic fracture in her mother. Blood pressure is 134/86 mm Hg and pulse is 72/min. BMI is 33 kg/m². Physical examination shows no abnormalities. Laboratory results show a hemoglobin A1c of 8.2%. After further discussion, a sodium-glucose cotransporter-2 inhibitor is added to the patient's drug regimen. Which of the following is the most likely additional effect of the newly prescribed medication?

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11ec160b_3bb2_afad_9249_9d8f78dfd211_MD0001_00 Sodium-glucose cotransporter 2 (SGLT2) is a low-affinity, high-capacity transport protein that is responsible for reabsorbing 90% of filtered glucose in the proximal renal tubule. SGLT2 inhibitors (eg, canagliflozin, dapagliflozin) are oral antidiabetic agents that decrease renal reabsorption of glucose and sodium. By decreasing glucose reabsorption, SGLT2 inhibitors lower blood glucose levels. Because the effect of SGLT2 inhibitors is dependent on the filtered glucose load, and because they do not stimulate insulin production, these medications are associated with a low risk of hypoglycemia. Patients may also experience weight loss due to glucose loss in the urine. In addition, the decreased reabsorption of sodium and glucose induces osmotic diuresis, which causes a small decrease in blood pressure. This effect is associated with a decreased risk for cardiovascular events and a lower rate of hospitalization for heart failure. However, the resulting hypovolemia can lead to orthostatic hypotension in some patients and may increase the risk for acute kidney injury. (Choice B) Due to the excess urinary glucose content, SGLT2 inhibitors are associated with an increased risk of genitourinary tract infections (eg, vaginitis, Fournier's gangrene). (Choice C) Decreased sodium resorption can lead to increased phosphate reabsorption in the distal tubule, which can stimulate secretion of parathyroid hormone and lead to decreased bone density. (Choice D) Thiazolidinediones (eg, pioglitazone) are antidiabetic medications that are associated with fluid retention, but the SGLT2 inhibitors induce net loss of fluid and sodium. (Choice E) Glucagon-like polypeptide-1 (GLP-1) regulates glucose by slowing gastric emptying and increasing glucose-dependent insulin release. Pharmacologic GLP-1 agonists (eg, exenatide) are parenteral agents used for management of type 2 diabetes that increase postprandial satiety and induce weight loss. Educational objective: Sodium-glucose cotransporter 2 inhibitors (eg, canagliflozin, dapagliflozin) decrease renal reabsorption of glucose and sodium, leading to lower blood glucose levels. The decreased reabsorption of sodium and glucose also induces osmotic diuresis, which causes a decrease in blood pressure. Excess urinary glucose also leads to an increased risk for genitourinary tract infections. __________ References: Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus. (http://www.ncbi.nlm.nih.gov/pubmed/27470878)

A 45-Year-Old Woman Comes to the Office for Follow-Up of Type