What are the best medication choices and dosage adjustments for a patient with impaired renal function, taking Lantus (insulin glargine) 16 units daily, with an A1C of 9%?

Medication Optimization for Uncontrolled Diabetes with Impaired Renal Function

You must immediately add metformin 500 mg twice daily and increase your Lantus insulin dose by 25-50% while closely monitoring for hypoglycemia, given the A1C of 9% indicates severely inadequate glycemic control.

Immediate Insulin Dose Adjustment

Your current Lantus 16 units daily is insufficient with an A1C of 9%. Increase Lantus to 20-24 units daily (a 25-50% increase) and titrate upward by 2-4 units every 3 days until fasting glucose reaches 80-130 mg/dL. 1

Critical Consideration for Renal Impairment

• If your eGFR is 30-44 mL/min/1.73m² (CKD stage 3b), reduce your total daily insulin dose by 25-30% from what would otherwise be prescribed to prevent hypoglycemia, as insulin clearance is significantly reduced 1
• If your eGFR is 15-29 mL/min/1.73m² (CKD stage 4), reduce total daily insulin by 50% 1
• If you have CKD stage 5 on dialysis, reduce total daily insulin by 35-40% and further reduce basal insulin by an additional 25% on pre-hemodialysis days 1
• Titrate conservatively and monitor glucose closely, as hypoglycemia risk increases substantially with declining renal function 1

Add Metformin Immediately

Start metformin 500 mg twice daily with meals, regardless of your renal function, unless your eGFR is below 30 mL/min/1.73m². 1, 2

Metformin Dosing by Renal Function

• eGFR ≥45 mL/min/1.73m²: No dose adjustment needed; can use up to 2000 mg daily 1
• eGFR 30-44 mL/min/1.73m²: Maximum 1000 mg daily 1
• eGFR <30 mL/min/1.73m²: Contraindicated—do not use 1

Metformin Safety in Renal Impairment

The historical fear of lactic acidosis with metformin in mild-moderate renal impairment is largely unfounded. The actual incidence of lactic acidosis is extremely low (7.4 per 100,000 person-years) and only becomes significantly elevated when eGFR drops below 60 mL/min/1.73m² AND high doses (>2g daily) are used 3, 4. Metformin remains the preferred first-line agent even with eGFR 30-45 mL/min/1.73m², just at reduced doses. 1, 4

Add an SGLT2 Inhibitor for Kidney and Cardiovascular Protection

If your eGFR is ≥20 mL/min/1.73m², add an SGLT2 inhibitor (dapagliflozin 10 mg daily, canagliflozin 100 mg daily, or empagliflozin 10 mg daily) for kidney protection and cardiovascular benefit, independent of glucose-lowering effects. 1

SGLT2 Inhibitor Dosing by Renal Function

• eGFR ≥45 mL/min/1.73m²: Full doses of any SGLT2 inhibitor 1
• eGFR 30-44 mL/min/1.73m²: Canagliflozin maximum 100 mg daily; dapagliflozin 10 mg daily; empagliflozin not recommended for initiation 1
• eGFR 20-29 mL/min/1.73m²: Only dapagliflozin can be initiated; continue others if already on them 1
• eGFR <20 mL/min/1.73m²: Do not initiate any SGLT2 inhibitor, but may continue dapagliflozin until dialysis if already tolerating 1

Critical SGLT2 Inhibitor Precautions

• Reduce basal insulin dose by 10-20% when starting an SGLT2 inhibitor to prevent hypoglycemia, though absolute risk is low 1
• Maintain at least low-dose insulin and pause SGLT2 inhibitor during acute illness to prevent euglycemic ketoacidosis 1
• Monitor for genital mycotic infections (6% incidence vs 1% placebo), which are usually easily treated 1

Consider Adding a GLP-1 Receptor Agonist

If A1C remains >8% after 3 months on metformin, insulin, and SGLT2 inhibitor, add a GLP-1 receptor agonist (dulaglutide, liraglutide, or semaglutide) as these require no dose adjustment for renal impairment. 1

• Dulaglutide, liraglutide, and semaglutide require no dose adjustment at any level of renal function 1
• Avoid exenatide if eGFR <30 mL/min/1.73m² and avoid lixisenatide if eGFR <30 mL/min/1.73m² 1

Avoid These Medications in Renal Impairment

• Never use glyburide (contraindicated in any renal impairment) due to severe hypoglycemia risk 1
• Avoid sulfonylureas entirely if possible given hypoglycemia risk; if absolutely necessary, use only glipizide 2.5 mg daily or glimepiride 1 mg daily with extreme caution 1
• Avoid acarbose and miglitol if eGFR <30 mL/min/1.73m² 1

Monitoring Requirements

• Check renal function (eGFR and creatinine) every 3-6 months when eGFR <60 mL/min/1.73m² 5
• Monitor vitamin B12 levels if on metformin >4 years 2, 5
• Check glucose 2-4 times daily while titrating insulin to prevent hypoglycemia 1
• Measure A1C every 3 months until target achieved, then every 6 months 1
• Note that A1C becomes unreliable in CKD stage 4-5 and dialysis; consider continuous glucose monitoring (CGM) or glucose management indicator (GMI) instead 1

Common Pitfalls to Avoid

• Do not continue insulin at the same dose when adding other glucose-lowering agents—reduce insulin by 10-20% to prevent hypoglycemia 1
• Do not stop SGLT2 inhibitors when eGFR declines below the initiation threshold—continue them for kidney protection until dialysis 1
• Do not use A1C alone for glucose monitoring in advanced CKD (stages 4-5)—it underestimates true glycemia due to anemia and altered red blood cell turnover 1
• Do not target A1C <7% if patient has limited life expectancy or high hypoglycemia risk—individualize targets based on comorbidities 1