A 76-year-old African American woman with a history of type 2 diabetes mellitus and chronic kidney disease is evaluated for an elevated A1c level of 7.6% (American Diabetes Association goal, <7%). Current medications include metformin, 1000 mg twice daily; glimepiride, 8 mg/d; lisinopril, 20 mg/d; carvedilol, 25 mg twice daily; furosemide, 40 mg twice daily; aspirin, 81 mg/d; and atorvastatin, 80 mg/d. Recent laboratory findings are significant for an estimated glomerular filtration rate (eGFR) of 50 mL/min/1.73 m2. The patient would like to try the “new diabetes drug” she saw advertised on TV, but you inform her that she cannot take canagliflozin at this time.
Answer: D. Canagliflozin is not recommended because of the patient’s risk for hypotension.
In patients uncontrolled with 2 oral medications, the new class of agents—sodium glucose cotransporter 2 (SGLT2) inhibitors, such as canagliflozin—have many advantages. They offer a new mechanism of action and are associated with a modest reduction in A1c level, a low risk of hypoglycemia, and weight loss.
They are not appropriate, however, for this patient who is at significant risk for hypotension. Through their mechanism of action, the SGLT2 inhibitors cause osmotic diuresis and intravascular volume contraction. As a result, symptomatic hypotension can occur; this has been noted particularly in patients receiving the 300-mg dose of canagliflozin. The prescribing information recommends monitoring the volume status in patients who have risk factors for hypotension. The 3 risk factors associated with symptomatic hypotension are the use of loop diuretics, moderate renal impairment (eGFR of 30 to less than 60 mL/min/1.73 m2), and age 75 years or older. This patient has all 3 risk factors and, therefore, an alternative agent is recommended at this time.
Choice A is not correct because in the CANTATA-MSU trial, canagliflozin decreased the A1c level by 0.71% and 0.92%, respectively, for the 100-mg and 300-mg doses when compared with placebo in patients uncontrolled on metformin and a sulfonylurea. Choice B is not correct because this drug can be used in moderate renal disease (eGFR between 45 and 60 mL/min/1.73 m2); however, the dose should be reduced to no higher than 100 mg/d. Choice C is incorrect because this drug has been studied and shown to be safe and effective in combination with metformin, metformin and sulfonylureas, and metformin and pioglitazone.