Is it advisable to discontinue nighttime insulin glargine (glargine) and administer it in the morning for an End-Stage Renal Disease (ESRD) patient on hemodialysis (HD) with diabetes, currently experiencing significant blood sugar fluctuations while on a regimen of glimperide (glimepiride) 1 mg tablet twice daily, novolog (insulin aspart) sliding scale, and insulin glargine 7 units at bedtime?

Switching Nighttime Glargine to Morning in ESRD Patient on Hemodialysis

Yes, switching insulin glargine from bedtime to morning administration is a reasonable and potentially safer strategy for this ESRD patient on hemodialysis who is experiencing recurrent hypoglycemia, but you should also strongly consider reducing or discontinuing the glimepiride, which is the primary culprit for the dangerous early morning hypoglycemic episodes (63-76 mg/dL). 1

Primary Concern: Recurrent Hypoglycemia Pattern

Your patient's glucose trends reveal a dangerous pattern:

• Early morning hypoglycemia: 63 mg/dL (1/5), 73 mg/dL (1/2), 76 mg/dL (1/3) 1
• Post-lunch hyperglycemia spike: 328 mg/dL (1/5) 1
• Otherwise relatively controlled values in the 98-142 mg/dL range

ESRD patients on hemodialysis are at markedly increased risk for hypoglycemia due to: decreased gluconeogenesis, reduced insulin clearance by the kidney (40% reduction in total daily insulin requirements in type 1 diabetes, 50% in type 2 diabetes), reduced insulin degradation, increased erythrocyte glucose uptake during hemodialysis, impaired counterregulatory hormone responses, and nutritional deprivation. 1

Recommended Medication Adjustments

1. Discontinue or Reduce Glimepiride (Priority Action)

The glimepiride 1 mg BID is likely the primary driver of early morning hypoglycemia and should be discontinued or at minimum reduced to once daily. 1

• Sulfonylureas like glimepiride carry significant hypoglycemia risk in ESRD patients 1
• The ADA/KDIGO consensus recommends initiating glimepiride conservatively at 1 mg daily and titrating slowly to avoid hypoglycemia in patients with eGFR <45 mL/min/1.73 m² 1
• Your patient is receiving 1 mg BID, which is excessive for ESRD 1
• The early morning lows (63-76 mg/dL) occur when overnight glimepiride effect overlaps with bedtime glargine 1

2. Switch Glargine from Bedtime to Morning

Morning administration of glargine is equally effective and may reduce nocturnal hypoglycemia risk. 2, 3

• FDA labeling data demonstrates that glargine administered pre-breakfast achieved similar HbA1c reductions compared to bedtime dosing in type 2 diabetes patients (mean change -1.3% vs -1.0% respectively) 2
• A study specifically in hemodialysis patients showed that switching from NPH to glargine improved glycemic control, reduced hypoglycemic episodes significantly, and improved quality of life 3
• Morning dosing allows peak insulin action during daytime meals when glucose monitoring is more frequent and carbohydrate intake is more predictable 1, 2
• The maximum mean blood glucose occurs just prior to glargine injection regardless of timing, so morning dosing will target daytime hyperglycemia 2

3. Consider Reducing Glargine Dose

Reduce the glargine dose by 10-20% (from 7 units to 5-6 units) when switching to morning administration, especially if discontinuing glimepiride. 1

• ADA guidelines recommend reducing basal insulin by 10-20% when hypoglycemia occurs without clear cause 1
• The algorithm for simplifying insulin in older adults (applicable to ESRD patients) recommends changing timing from bedtime to morning and titrating based on fasting glucose goal of 90-150 mg/dL 1
• Target fasting glucose of 110 mg/dL is appropriate for ESRD patients to balance hypoglycemia risk 3

4. Maintain Novolog Sliding Scale

Continue the Novolog sliding scale for prandial coverage, particularly for the 328 mg/dL post-lunch spike. 1

• The isolated post-lunch hyperglycemia (328 mg/dL) suggests inadequate prandial coverage for that meal 1
• Consider adding a fixed small dose (2-4 units) of Novolog before lunch if the spike persists 1
• Simplified sliding scale for ESRD: give 2 units rapid-acting insulin for premeal glucose >250 mg/dL, 4 units for >350 mg/dL 1

Monitoring Strategy

Implement frequent glucose monitoring during the transition period:

• Check fasting glucose daily for 1 week to titrate morning glargine 1, 3
• If 50% of fasting values are >150 mg/dL, increase glargine by 2 units 1
• If >2 fasting values per week are <90 mg/dL, decrease glargine by 2 units 1
• Monitor pre-lunch and pre-dinner glucose to assess prandial insulin needs 1
• Consider continuous glucose monitoring (CGM) if available, as it has been shown to decrease patient burden, improve adherence, reduce hypoglycemia, and improve quality of life in ESRD patients on hemodialysis 4

Common Pitfalls to Avoid

Do not simply switch glargine timing without addressing the glimepiride - the sulfonylurea is likely the primary cause of early morning hypoglycemia in this patient 1

Do not maintain the same glargine dose when switching timing - reduce by 10-20% initially and titrate based on response 1

Do not ignore the isolated post-lunch hyperglycemia spike - this requires targeted prandial insulin coverage 1

Avoid aggressive glycemic targets in ESRD - aim for fasting glucose 90-150 mg/dL rather than tight control, as both very high HbA1c (≥8.5%) and very low HbA1c (≤5.4%) are associated with increased mortality in hemodialysis patients 1