What is the initial medication for a patient with type 2 diabetes (T2D) and Chronic Kidney Disease (CKD) stage 5 with Impaired Renal Function, not currently on any diabetic medications?

Medication Management for Type 2 Diabetes with CKD Stage 5 (GFR 17)

For a patient with type 2 diabetes and CKD with GFR of 17 ml/min/1.73m², a GLP-1 receptor agonist should be initiated as first-line therapy due to the severe renal impairment that precludes the use of metformin and SGLT2 inhibitors. 1, 2, 3

Medication Selection Algorithm

First-Line Therapy

• GLP-1 receptor agonists are the preferred first-line agents for patients with type 2 diabetes and GFR <20 ml/min/1.73m² as they maintain glucose-lowering efficacy in advanced CKD and provide cardiovascular benefits 1, 2
• Specific GLP-1 RAs that can be used in severe CKD include liraglutide, dulaglutide, and semaglutide (avoid exenatide which is not recommended in severe CKD) 2, 3

Medications to Avoid at GFR 17

• Metformin is contraindicated at GFR <30 ml/min/1.73m² due to increased risk of lactic acidosis 1
• SGLT2 inhibitors are not recommended for initiation when GFR <20 ml/min/1.73m² due to diminished glycemic efficacy 1, 2
• First-generation sulfonylureas should be avoided altogether in advanced CKD due to high risk of prolonged hypoglycemia 2, 4

Dose Adjustments and Monitoring

• If using insulin therapy (which may be necessary in advanced CKD), dose reductions of 25% or more are typically required when GFR <45 ml/min/1.73m² due to decreased insulin clearance 2, 5
• If glycemic targets are not achieved with GLP-1 RA, consider adding DPP-4 inhibitors (preferably linagliptin which requires no dose adjustment in renal impairment) 2, 4
• Monitor HbA1c every 3-6 months, with awareness that HbA1c may be less accurate in advanced CKD 3

Comprehensive Management

• Initiate or continue RAS blockade (ACEi or ARB) if the patient has hypertension and albuminuria, with careful monitoring of potassium and creatinine 2, 3
• Add statin therapy regardless of baseline lipid levels to reduce cardiovascular risk 2, 3
• Consider nonsteroidal mineralocorticoid receptor antagonist (finerenone) if albuminuria is present and serum potassium is normal 3, 6

Potential Pitfalls and Cautions

• Hypoglycemia risk increases substantially in CKD stage 5 due to decreased renal gluconeogenesis and reduced clearance of insulin and oral agents 2, 4
• If using sulfonylureas, glipizide is preferred as it does not have active metabolites that accumulate in renal failure 2, 5
• Continuous glucose monitoring may be beneficial when HbA1c is unreliable due to advanced CKD 3
• Evaluate for volume depletion risk with any medication changes, especially if the patient is on diuretics 2

Follow-up and Monitoring

• Monitor kidney function every 3-6 months when GFR <60 ml/min/1.73m² 3
• Assess for albuminuria regularly as it is an important marker of kidney disease progression 3, 7
• Consider referral to nephrology for co-management, especially as the patient approaches the need for kidney replacement therapy 8, 7