What adjustments should be made to the medication regimen of a patient with impaired renal function (eGFR of 28 ml/min/1.73m^2) who is currently taking metformin and sitagliptin for glucose control?

Medication Adjustments for eGFR 28 mL/min/1.73m²

Immediate Action Required: Discontinue Metformin

Metformin must be stopped immediately in this patient with eGFR 28 mL/min/1.73m², as it is contraindicated below 30 mL/min/1.73m² due to risk of life-threatening lactic acidosis. 1, 2

Metformin Management

• Discontinue metformin completely - FDA labeling explicitly contraindicates metformin when eGFR <30 mL/min/1.73m², as metformin accumulation substantially increases lactic acidosis risk 2
• The risk of metformin-associated lactic acidosis increases with severity of renal impairment because metformin is substantially excreted by the kidney 2
• Postmarketing cases of metformin-associated lactic acidosis primarily occurred in patients with significant renal impairment 2

Sitagliptin: Continue Without Dose Adjustment

Sitagliptin can be safely continued at standard dosing (typically 100 mg daily) without any dose adjustment, as DPP-4 inhibitors like sitagliptin do not require modification at any level of renal function. 3

Sitagliptin Management

• Sitagliptin (and linagliptin) require no dose adjustment in any stage of renal disease, including end-stage renal disease 3
• Sitagliptin has demonstrated efficacy and safety in older patients with mild renal insufficiency 4

Add SGLT2 Inhibitor for Kidney and Cardiovascular Protection

Despite the eGFR of 28 mL/min/1.73m², an SGLT2 inhibitor should be initiated immediately, as current guidelines recommend SGLT2 inhibitors for patients with eGFR ≥20 mL/min/1.73m² to slow CKD progression and reduce heart failure risk independent of glucose management. 1

SGLT2 Inhibitor Rationale

• SGLT2 inhibitors are recommended for people with eGFR ≥20 mL/min/1.73m² and type 2 diabetes, as they slow CKD progression and reduce heart failure risk independent of glucose management 1
• These agents reduce renal tubular glucose reabsorption, weight, systemic blood pressure, intraglomerular pressure, and albuminuria through mechanisms independent of glycemia 1
• SGLT2 inhibitors reduce oxidative stress in the kidney and blunt increases in angiotensinogen as well as reduce NLRP3 inflammasome activity 1
• Clinical trials (CREDENCE with canagliflozin and DAPA-CKD with dapagliflozin) demonstrated significant benefit for composite outcomes including substantial eGFR decline, kidney failure, and mortality 1

Consider GLP-1 Receptor Agonist for Additional Protection

A GLP-1 receptor agonist (such as semaglutide, liraglutide, or dulaglutide) should be strongly considered as they reduce cardiovascular events, slow CKD progression, and can be used with eGFR >15 mL/min/1.73m² without dose adjustment. 1, 3

GLP-1 RA Benefits

• GLP-1 RAs reduce risks of CVD events and hypoglycemia and slow progression of CKD 1
• These agents can be used with eGFR >15 mL/min/1.73m² without dose adjustment, providing cardiovascular and potential renal benefits 3
• Semaglutide can be used as a first-line agent for people with CKD 1

Monitoring Requirements

Monitor renal function (serum creatinine and eGFR) every 3-6 months, or more frequently if clinically indicated, and assess HbA1c every 3 months after medication changes. 5, 3

Specific Monitoring Parameters

• Monitor serum creatinine and eGFR every 3-6 months in patients with eGFR <60 mL/min/1.73m² 5, 3
• Monitor electrolytes (potassium, sodium) frequently, especially if using RAAS blockers or diuretics 5
• Assess HbA1c every 3 months to evaluate glycemic control after medication changes 3

Alternative Glucose-Lowering Options if Needed

If additional glucose lowering is required beyond sitagliptin and SGLT2 inhibitor:

• Insulin remains safe and effective at all levels of renal function without dose adjustment based on eGFR alone, though doses may need reduction due to decreased renal insulin clearance requiring close glucose monitoring 3
• Other DPP-4 inhibitors like linagliptin (5 mg daily) require no dose adjustment at any level of renal function 3

Critical Pitfalls to Avoid

• Never continue metformin with eGFR <30 mL/min/1.73m² - this is an absolute contraindication due to lactic acidosis risk 1, 2
• Do not withhold SGLT2 inhibitors based on the misconception they only work for glucose control - their kidney and cardiovascular benefits are independent of glycemic effects 1
• Temporarily discontinue metformin (if eGFR were higher) before iodinated contrast procedures in patients with eGFR 30-60 mL/min/1.73m² 1, 2