What is the recommended initial dose of glargine (insulin glargine) for a diabetic patient with severe renal impairment and a weight of 58 kg?

Insulin Glargine Dosing in Severe Renal Impairment

For this patient with severe renal impairment (eGFR 14 mL/min/1.73 m², creatinine 409 μmol/L), start insulin glargine at 5-6 units once daily (approximately 0.1 units/kg for a 58 kg patient), which represents a 50% reduction from standard initial dosing due to the dramatically increased hypoglycemia risk in advanced chronic kidney disease. 1

Critical Dosing Adjustments for Severe Renal Impairment

Initial Dose Calculation

• The standard starting dose for insulin-naive type 2 diabetes patients is 10 units once daily or 0.1-0.2 units/kg/day, but this patient requires substantial dose reduction 1
• For patients with CKD Stage 5 (eGFR <15 mL/min/1.73 m²) and type 2 diabetes, reduce the total daily insulin dose by 50% 1
• For this 58 kg patient, calculate: 0.1 units/kg × 58 kg = 5.8 units, rounded to 5-6 units once daily as the initial dose 1
• Use the lower end of dosing ranges (0.1 units/kg/day) for high-risk patients with severe renal impairment, rather than 0.2 units/kg/day 1

Physiological Rationale for Dose Reduction

• Insulin clearance decreases dramatically with declining kidney function, resulting in prolonged insulin activity and substantially increased hypoglycemia risk 1
• Patients with severe renal impairment have a fivefold higher incidence of severe hypoglycemic episodes (1.28 vs 0.25 cases/patient-year) compared to those with normal kidney function 2
• The risk of hypoglycemia and duration of insulin activity increases proportionally with the severity of impaired kidney function 1

Titration Protocol for Severe Renal Impairment

Conservative Titration Schedule

• Increase the dose by only 1-2 units every 5-7 days (not the standard 3 days) based on fasting glucose patterns, targeting 80-130 mg/dL 1
• Monitor fasting blood glucose daily during titration, with more frequent monitoring than in patients with normal renal function 1, 3
• If hypoglycemia occurs without clear cause, immediately reduce the dose by 20% (not just 10-20%) 1
• Assess kidney function before any dose increases, as declining eGFR fundamentally changes insulin requirements 3

Maximum Dose Considerations

• When basal insulin approaches 0.3-0.4 units/kg/day (17-23 units for this patient) without achieving glycemic targets, consider adding prandial insulin rather than continuing to escalate basal insulin alone 1
• The critical threshold of 0.5 units/kg/day for overbasalization applies even more stringently in severe renal impairment due to accumulation risk 1

Enhanced Monitoring Requirements

Hypoglycemia Surveillance

• Check blood glucose at least 4 times daily: fasting, pre-lunch, pre-dinner, and bedtime 1
• Patients with severe renal impairment are at increased risk of hypoglycemia unawareness, which may develop with repeated episodes 3
• Scrupulous avoidance of hypoglycemia for 2-3 weeks can reverse hypoglycemia unawareness if present 1
• Treat any glucose <70 mg/dL immediately with 15 grams of fast-acting carbohydrate 1

Renal Function Monitoring

• Reassess eGFR and creatinine before any dose adjustments, as further decline in kidney function requires additional dose reductions 3
• Monitor for signs of insulin accumulation: unexplained hypoglycemia, prolonged glucose-lowering effect, or increased glucose variability 1

Administration and Timing

Optimal Dosing Schedule

• Administer insulin glargine at the same time each day to maintain stable blood glucose levels 3
• Although typically given at bedtime, morning administration may be preferable in severe renal impairment to allow daytime monitoring for hypoglycemia 4, 5
• In some patients with severe renal impairment, glargine may not provide full 24-hour coverage and may require twice-daily dosing at lower individual doses 3

Foundation Therapy Considerations

Metformin Contraindication

• Metformin is contraindicated with eGFR <30 mL/min/1.73 m² due to lactic acidosis risk 6
• This patient (eGFR 14) should not be on metformin and requires insulin as primary therapy 6

Oral Agent Adjustments

• Most oral antidiabetic drugs become inappropriate as kidney dysfunction progresses to Stage 4-5 CKD 7
• Sulfonylureas like glipizide should be avoided or used with extreme caution in eGFR <30 mL/min/1.73 m², as they dramatically increase hypoglycemia risk 8

Critical Pitfalls to Avoid

Dosing Errors

• Never use standard initial dosing (10 units or 0.2 units/kg/day) in severe renal impairment, as this leads to severe hypoglycemia 1, 2
• Never titrate aggressively (4 units every 3 days) as recommended for patients with normal kidney function 1
• Never continue escalating basal insulin beyond 0.3-0.4 units/kg/day without addressing postprandial hyperglycemia with prandial insulin 1

Monitoring Failures

• Never delay dose reduction when hypoglycemia occurs—75% of hospitalized patients who experienced hypoglycemia had no insulin dose adjustment before the next administration 1
• Never ignore declining eGFR when adjusting insulin doses, as this fundamentally changes insulin clearance and requirements 3

Expected Outcomes

Glycemic Control

• Treatment with glargine-based basal insulin therapy in Stage 4 CKD achieves 1.2% (13.2 mmol/mol) HbA1c reduction without significant weight change 7
• Fasting and postprandial glucose values improve significantly with appropriate dosing 7

Safety Profile

• With conservative dosing (starting at 5-6 units), hypoglycemia rates remain manageable, though approximately 34% of patients may experience documented hypoglycemia 7
• Severe hypoglycemia occurs in approximately 28% of those with any hypoglycemia, emphasizing the need for vigilant monitoring 7
• No significant changes in weight, blood pressure, or eGFR occur during treatment 7

Patient Education Essentials

• Teach recognition and immediate treatment of hypoglycemia with 15 grams of fast-acting carbohydrate 1
• Emphasize the importance of consistent meal timing and carbohydrate intake 1
• Provide clear instructions on when to contact healthcare providers: persistent fasting glucose >180 mg/dL after 2-3 weeks, any severe hypoglycemia, or symptoms of hypoglycemia unawareness 1
• Ensure proper insulin injection technique and site rotation 1