SGLT2 inhibitor for proteinuric DKD on maximal ACE inhibitor

Question

A 58-year-old woman with CKD stage 3, type 2 diabetes mellitus, hypertension, and hyperlipidemia presents to the outpatient clinic for routine follow-up. She feels well and has no complaints. Current medications include atorvastatin, hydrochlorothiazide, maximum dose lisinopril, and metformin. On exam, BP is 130/78 mm Hg and heart rate is 72/min. Weight is 75 kg, and body mass index is 34 kg/m². She has trace lower extremity edema. The remainder of her examination is unremarkable. Laboratory data: sodium 137 mEq/L (reference 136–145); potassium 5.2 mEq/L (3.5–5.0); chloride 102 mEq/L (98–106); CO₂ 24 mEq/L (23–28); BUN 35 mg/dL (8–20); creatinine 1.4 mg/dL (0.5–1.1); glucose 153 mg/dL (70–99, fasting); eGFR 46 mL/min/1.73 m² (≥60); hemoglobin A1c 7.9% (4.0–5.6); urine protein-to-creatinine ratio 1.9 mg/mg (<0.2). Which of the following is the MOST APPROPRIATE medication to preserve kidney function?

Accepted Answer

C. Dapagliflozin — The next most appropriate medication to prescribe for this patient is dapagliflozin. This patient would benefit from starting dapagliflozin, a sodium-glucose cotransporter type 2 inhibitor (SGLT2i). SGLT2is have been shown to reduce albuminuria, slow the rate of eGFR decline, and delay progression to ESRD. This patient is prescribed a maximal dose of ACEI and continues to have substantial proteinuria (urine protein-to-creatinine ratio of 1.9 mg/mg). Her glycemic control is also suboptimal, so she would benefit from adding an SGLT2i. These medications also confer significant cardiovascular benefits in patients with proteinuric CKD, with and without diabetes, and congestive heart failure.

Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that would also provide glycemic control. Studies of GLP-1 receptor agonists have also demonstrated substantial improvements in albuminuria. Semaglutide was recently shown to improve kidney and cardiovascular outcomes in a large-scale clinical trial, but such data are not available for liraglutide, and the body of evidence for the benefit of SGLT2i is much more robust than for GLP-1 receptor agonists at this time. Most clinicians would initiate SGLT2i before GLP-1 receptor agonists to manage diabetic kidney disease. Other hypoglycemic agents that have been shown to reduce albuminuria include dipeptidyl-peptidase-4 (DPP-4) inhibitors and thiazolidinediones, but neither of these classes of medications have demonstrated reduction in the rate of eGFR decline or progression to ESRD.

Adding insulin therapy would improve glycemic control. Tight glycemic control can reduce albuminuria, but insulin therapy has not been shown to slow the progression of diabetic kidney disease.

Spironolactone has been shown to reduce proteinuria when added to treatment with ACEI or ARB. However, this patient would be at risk for hyperkalemia, as her serum potassium is already mildly elevated. Furthermore, spironolactone would not improve glycemic control. Studies with finerenone, a nonsteroidal mineralocorticoid receptor blocker (MRB), show evidence of clinical benefit for kidney outcomes, but whether this benefit is a class effect that extends to other MRBs remains to be determined.

SGLT2 inhibitor for proteinuric DKD on maximal ACE inhibitor

Explanation

Why each option

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