MKSAP quiz: Declining kidney function
This month's quiz asks readers to evaluate a 67-year-old woman with type 2 diabetes, diabetic nephropathy, and retinopathy, and choose a medication management strategy.
A 67-year-old woman is evaluated for management of her type 2 diabetes mellitus, which was diagnosed 15 years ago. She also has diabetic nephropathy (urine albumin-creatinine ratio >300 mg/g) and retinopathy. She does not have hypoglycemia. Medications are enalapril, atorvastatin, insulin glargine, insulin aspart, and metformin.
On physical examination, vital signs are normal. BMI is 26. Ophthalmoscopic examination shows nonproliferative diabetic retinopathy. The remainder of the physical examination is unremarkable.
Laboratory studies show a hemoglobin A1c level of 7.7% and serum creatinine level of 1.4 mg/dL (123.8 µmol/L). She has had a gradual decline in her estimated glomerular filtration rate (eGFR) from 50 to 39 mL/min/1.73 m2 over the last 5 years.
Which of the following is the most appropriate management?
A. Add empagliflozin
B. Continue current regimen
C. Discontinue metformin
D. Increase insulin glargine
MKSAP Answer and Critique
The correct answer is A. Add empagliflozin. This item is available to MKSAP 18 subscribers as item 10 of extension set 4 in the Endocrinology and Metabolism section. More information about MKSAP 18 is available online.
The most appropriate management of this patient's diabetes mellitus is to add empagliflozin to her current regimen. The 2020 American Diabetes Association Standards of Medical Care for Patients with Diabetes states that physicians should consider use of a sodium–glucose cotransporter-2 (SGLT2) inhibitor in patients with an estimated glomerular filtration rate (eGFR) greater than 30 mL/min/1.73 m2 and urine albumin-creatinine ratio greater than 30 mg/g, particularly in those with urine albumin-creatinine ratio greater than 300 mg/g, to reduce risk for chronic kidney disease (CKD) progression, cardiovascular events, or both. In patients with CKD who are at increased risk for cardiovascular events, use of a glucagon-like peptide 1 receptor agonist may reduce risk for progression of albuminuria, cardiovascular events, or both. Use of SGLT2 inhibitors reduces cardiovascular and kidney events in patients with eGFR as low as 30 mL/min/1.73 m2 independently of glucose-lowering effects.
The FDA previously considered serum creatinine levels of 1.4 mg/dL (123.8 µmol/L) or higher in women and 1.5 mg/dL (132.6 µmol/L) or higher in men a contraindication to metformin use due to concerns for development of lactic acidosis. After further review of safety data from multiple studies, the FDA revised the criteria for continued safe use of metformin. To better estimate kidney function, eGFR replaced serum creatinine level in the determination of safe use of metformin. Patients with a decrease in eGFR to 30 to 45 mL/min/1.73 m2 while treated with metformin may continue its use after consideration of harms and benefits. If metformin is continued, a 50% dose reduction should be considered, and frequent monitoring of kidney function (every 3 months) is recommended. Metformin should be discontinued if the eGFR falls below 30 mL/min/1.73 m2.
Less stringent A1C goals (such as <8%) may be appropriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced microvascular or macrovascular complications, extensive comorbid conditions, or longstanding diabetes in whom the goal is difficult to achieve. This is an older patient with multiple comorbidities and advanced microvascular disease. She is at her goal hemoglobin A1c level of less than 8% per the American Diabetes Association guidelines with her current regimen. Because she is at her goal hemoglobin A1c level, intensifying her therapy with increased insulin glargine is unnecessary. In addition, increasing the insulin glargine dose in the setting of worsening kidney function could increase the risk for hypoglycemia and does not slow the progression of CKD.
Key Point
- The use of a sodium–glucose cotransporter-2 inhibitor should be considered in patients with an estimated glomerular filtration rate greater than 30 mL/min/1.73 m2 and urine albumin-creatinine ratio greater than 30 mg/g, particularly in those with urine albumin-creatinine ratio greater than 300 mg/g, to reduce risk for chronic kidney disease progression and cardiovascular events.