A 53-year-old man comes to the office due to uncontrolled type 2 diabetes mellitus. Three years ago, the patient was diagnosed with diabetes and started on metformin and lifestyle modification. In the past year, his hemoglobin A1c level has been steadily rising. Blood pressure is 145/90 mm Hg. BMI is 37 kg/m². Laboratory results are normal except for a fasting plasma glucose of 155 mg/dL and a hemoglobin A1c level of 8%. Additional treatment with canagliflozin is initiated. Over the next several days, which of the following changes are most likely to occur in this patient due to the new medication?

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11ec160b_3bb5_47c4_9249_c1d1d6b1dcea_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. Glucose reabsorption by SGLT2 is driven by cotransport of sodium, which occurs down its concentration gradient. The sodium is actively pumped across the basolateral membrane by Na-K-ATPase, and glucose follows by facilitated diffusion via glucose transporter-2. SGLT2 inhibitors (eg, canagliflozin, dapagliflozin) are oral antidiabetic agents that have the following effects: Decreased renal reabsorption of glucose, leading to increased urinary glucose excretion and lower blood glucose levels Natriuresis and osmotic diuresis due to decreased reabsorption of sodium and glucose, leading to a small decrease in extracellular fluid volume, total body sodium content, and blood pressure Decreased sodium reabsorption and increased sodium delivery to the macula densa, leading to decreased activation of the renin-angiotensin-aldosterone system, lower glomerular (and systemic) pressures, and delayed progression of nephropathy Educational objective: Sodium-glucose cotransporter 2 inhibitors decrease renal reabsorption of glucose and sodium, leading to increased urinary glucose excretion and decreased blood glucose levels. In addition, natriuresis and osmotic diuresis lead to a small decrease in extracellular fluid volume, total body sodium content, and blood pressure. __________ References: SGLT2 inhibitors with cardiovascular benefits: transforming clinical care in type 2 diabetes mellitus. (http://www.ncbi.nlm.nih.gov/pubmed/29196150)

A 53-Year-Old Man Comes to the Office Due to Uncontrolled