A 65-year-old woman comes to the clinic for follow up of type 2 diabetes mellitus. Medical history is notable for hypertension, stable coronary artery disease, and heart failure with preserved ejection fraction. Blood pressure is 144/95 mm Hg. Physical examination shows no murmurs, and the lungs are clear on auscultation. Fasting glucose is 122 mg/dL and hemoglobin A1c is 7.8%. The remainder of the laboratory results, including hepatic and renal markers, are normal. The patient is given a prescription for canagliflozin. She should be counseled on which of the following potential complications prior to initiation of this medication?

Question

A 65-year-old woman comes to the clinic for follow up of type 2 diabetes mellitus.  Medical history is notable for hypertension, stable coronary artery disease, and heart failure with preserved ejection fraction.  Blood pressure is 144/95 mm Hg.  Physical examination shows no murmurs, and the lungs are clear on auscultation.  Fasting glucose is 122 mg/dL and hemoglobin A1c is 7.8%.  The remainder of the laboratory results, including hepatic and renal markers, are normal.  The patient is given a prescription for canagliflozin.  She should be counseled on which of the following potential complications prior to initiation of this medication?

Quizplus · Accepted Answer

11ec160b_3ba9_87db_9249_5baf7b529037_MD0001_00 Sodium-glucose cotransporter 2 (SGLT2) is a high-capacity transport protein that reabsorbs 90% of filtered glucose in the proximal tubule. SGLT2 inhibitors (eg, canagliflozin, dapagliflozin) are oral antidiabetic agents that decrease renal reabsorption of glucose, leading to urinary glucose loss and decreased blood glucose levels. The decreased reabsorption of sodium and glucose also induces osmotic diuresis, leading to a decrease in blood pressure and a lower rate of hospitalization for heart failure. However, the glycosuria induced by SGLT2 inhibitors creates a more favorable environment for pathogenic bacteria and fungi in the genitourinary tract and perineum. This leads to an increased risk for urinary tract infections (eg, pyelonephritis), genital mycotic infections (eg, vaginitis), and necrotizing fasciitis of the perineum (Fournier gangrene). Other adverse effects include hypovolemia, which can lead to orthostatic hypotension and acute kidney injury. (Choice A) Thiazolidinediones (eg, pioglitazone) increase the reabsorption of sodium in the renal collecting tubule; this can lead to significant fluid retention, particularly in patients with heart failure. In contrast, SGLT2 inhibitors reduce fluid retention. (Choices B and E) Exogenous insulin and sulfonylureas, which stimulate endogenous insulin secretion, can cause hypoglycemia and weight gain. SGLT2 inhibitors carry a low risk of hypoglycemia because the glucose-lowering effect is proportionate to the filtered glucose load; also, renal glucose wasting typically induces mild weight loss. (Choice C) Metformin inhibits hepatic gluconeogenesis, leading to the accumulation of lactate. Patients with decreased lactate clearance (eg, renal or hepatic dysfunction, congestive heart failure) can have excessive accumulation of lactate, leading to lactic acidosis. Educational objective: Sodium-glucose cotransporter 2 inhibitors (eg, canagliflozin, dapagliflozin) decrease renal reabsorption of glucose, leading to urinary glucose loss and decreased blood glucose levels. However, the resulting glycosuria can lead to genitourinary tract infections and necrotizing fasciitis of the perineum. __________ References: Risks associated with SGLT2 inhibitors: an overview. (http://www.ncbi.nlm.nih.gov/pubmed/29485006)

A 65-Year-Old Woman Comes to the Clinic for Follow Up of Type