A 56-year-old man with type 2 diabetes mellitus, hypertension, and hyperlipidemia comes to the office due to elevated blood glucose levels. The patient's current medications include metformin, lisinopril, and simvastatin. Blood pressure is 150/90 mm Hg and pulse is 88/min. BMI is 37 kg/m². Physical examination is unremarkable. Laboratory studies show a fasting glucose level of 156 mg/dL, serum creatinine of 1.1 mg/dL, hemoglobin A1c of 8.1%, and urine albumin-creatinine ratio of 200 mg/g (normal:

Question

A 56-year-old man with type 2 diabetes mellitus, hypertension, and hyperlipidemia comes to the office due to elevated blood glucose levels. The patient's current medications include metformin, lisinopril, and simvastatin. Blood pressure is 150/90 mm Hg and pulse is 88/min. BMI is 37 kg/m². Physical examination is unremarkable. Laboratory studies show a fasting glucose level of 156 mg/dL, serum creatinine of 1.1 mg/dL, hemoglobin A1c of 8.1%, and urine albumin-creatinine ratio of 200 mg/g (normal: <30). Treatment with empagliflozin is initiated. Which of the following effects is most likely to be seen with this new treatment?

Quizplus · Accepted Answer

11ec160b_3bb5_95e5_9249_871c6167e0be_MD0001_00 This patient has incipient diabetic nephropathy with moderately increased albuminuria (ie, 30-300 mg/g). Although patients with more advanced diabetic kidney disease typically have reduced glomerular filtration (rising serum creatinine), in earlier stages, filtration is normal to increased and serum creatinine may be normal. In the kidneys, filtered glucose is normally reabsorbed with sodium by sodium-glucose cotransporter 2 (SGLT2) in the proximal tubule. In patients with diabetes, the excess filtered glucose load causes increased reabsorption of sodium by SGLT2. This results in decreased sodium delivery to the macula densa, stimulating renin secretion by the juxtaglomerular apparatus and, ultimately, increasing angiotensin II levels. Angiotensin II induces relative vasoconstriction in the renal efferent arterioles, increasing hydrostatic pressure in the glomerular capillaries and causing hyperfiltration. SGLT2 inhibitors (eg, empagliflozin) decrease the reabsorption of glucose and sodium in the proximal tubule, causing urine glucose wasting and lowering blood glucose. They also increase sodium delivery to the macula densa, which leads to decreased renin secretion, lower glomerular pressures, reduced hyperfiltration, and delayed progression of nephropathy. (Choice A) Glucose is absorbed in the intestine primarily via SGLT1 (not SGLT2), which is not significantly affected by empagliflozin. (Choices B and C) Most patients on SGLT2 inhibitors experience modest weight loss, not gain, due to urinary glucose wasting and lower circulating insulin levels. SGLT2 inhibitors lower blood glucose, leading to decreased secretion of insulin by pancreatic beta cells. (Choice E) SGLT2 inhibitors are associated with increased, not suppressed, glucagon secretion, possibly due to lower glucose and insulin levels or a direct effect on pancreatic alpha cells. Educational objective: In patients with diabetes, excess glucose in the proximal tubule causes increased reabsorption of sodium by sodium-glucose cotransporter 2 (SGLT2). This leads to decreased delivery of sodium to the macula densa and increased secretion of renin, ultimately increasing glomerular filtration pressure and causing hyperfiltration. SGLT2 inhibitors increase the delivery of sodium to the macula densa, decreasing renin production and reducing hyperfiltration. __________ References: SGLT2 inhibition and kidney protection. (http://www.ncbi.nlm.nih.gov/pubmed/29954951)

A 56-Year-Old Man with Type 2 Diabetes Mellitus, Hypertension, and Hyperlipidemia