Version July 2025
A1C: glycated hemoglobin; ACE: angiotensin-converting enzyme; ARB: angiotensin receptor blocker; eGFR: estimated glomerular filtration rate; GLP-1: glucagon-like peptide 1; MRA: mineralocorticoid receptor antagonist; SGLT2: sodium-glucose cotransporter 2; UACR: urine albumin-to-creatinine ratio.
* Most patients with diabetic kidney disease should also be treated with an ACE inhibitor or ARB. Refer to the UpToDate algorithm on overview of the management of diabetic kidney disease.
¶ When starting an MRA in patients with diabetic kidney disease, many experts and guideline panels suggest finerenone, a nonsteroidal MRA, based upon its proven efficacy compared with placebo in randomized trials. However, although it produces less hyperkalemia, finerenone is less effective in lowering blood pressure and is more expensive than spironolactone or eplerenone, and therefore some experts initiate spironolactone or eplerenone instead, particularly in patients with uncontrolled blood pressure, if serum potassium is ≤4.8 mEq/L and eGFR is not substantially reduced.
Δ If a GLP-1 receptor agonist is initiated after an SGLT2 inhibitor, we usually wait to start it until the patient has been on the SGLT2 inhibitor for at least 1 month (to monitor for adverse effects). For dosing of GLP-1 receptor agonists, refer to UpToDate content on treatment of diabetic kidney disease.
◊ GLP-1 receptor agonists should be avoided in patients with a history of pancreatitis and in those with a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia. In addition, GLP-1 receptor agonists can exacerbate gastroparesis, and patients with this condition may reasonably choose to not take a GLP-1 receptor agonist. If a GLP-1 receptor agonist is initiated in a patient with controlled A1C who is using insulin, the dose of insulin may need to be reduced; refer to UpToDate content on management of patients with type 2 diabetes for details.
§ If an SGLT2 inhibitor is initiated after a GLP-1 receptor agonist, we usually wait to start it until the patient has been on the GLP-1 receptor agonist for at least 1 month (to monitor for adverse effects). For dosing of SGLT2 inhibitors, refer to UpToDate content on treatment of diabetic kidney disease.
¥ SGLT2 inhibitors increase the risk of genital infections and may also be associated with a higher incidence of lower limb amputations (although such complications are uncommon). Patients with a prior history of or risk factors for genital infections or lower limb amputation may reasonably choose to not take an SGLT2 inhibitor. In addition, SGLT2 inhibitors should not be initiated in patients with eGFR <20 mL/min/1.73 m2. SGLT2 inhibitors can cause normoglycemic diabetic ketoacidosis, particularly in patients who become acutely ill, hypovolemic, or during periods of starvation.
