What medication is recommended for hyperglycemia at bedtime?

Management of Bedtime Hyperglycemia

For high blood sugar at bedtime, administer basal insulin (NPH, glargine, or detemir) at bedtime rather than rapid-acting insulin, which should never be used at this time. 1

Immediate Medication Recommendations

Basal Insulin Options for Bedtime Administration

• NPH insulin or long-acting basal analogs (glargine, detemir, degludec) are the appropriate choices for bedtime hyperglycemia, as they work to restrain hepatic glucose production overnight and control fasting glucose 1

• Starting dose should be 10 units once daily or 0.1-0.2 units/kg body weight for insulin-naive patients with type 2 diabetes 1, 2

• For patients with more severe hyperglycemia (blood glucose ≥300-350 mg/dL or A1C ≥9%), consider higher starting doses of 0.3-0.5 units/kg/day 1, 2

Critical Safety Rule

• Do not use rapid- or short-acting insulin at bedtime 1

• Rapid-acting insulins (lispro, aspart, glulisine) and short-acting insulin (regular) are designed for mealtime use only and should be administered 0-15 minutes before meals, not after eating or at bedtime 1

Timing Considerations for Basal Insulin

Bedtime vs. Morning Administration

• Insulin glargine can be administered at bedtime, before dinner, or in the morning with similar overall glycemic control, though the timing affects when blood glucose peaks occur 3, 4

• Bedtime administration of glargine may cause early-night hyperglycemia (22:00-02:00 hours), which can be improved by giving it at dinner-time or morning 5

• For older adults, consider changing basal insulin timing from bedtime to morning to simplify regimens and reduce nocturnal hypoglycemia risk 1

• Detemir should be administered with the evening meal or at bedtime for once-daily dosing; for twice-daily dosing, the evening dose can be given with the evening meal, at bedtime, or 12 hours after the morning dose 6

Dose Titration Algorithm

Standard Titration Protocol

• Increase basal insulin by 2 units every 3 days if fasting glucose is 140-179 mg/dL 1, 2

• Increase by 4 units every 3 days if fasting glucose is ≥180 mg/dL 1, 2

• Target fasting plasma glucose of 80-130 mg/dL (4.4-7.2 mmol/L) 1, 2

• If more than 2 fasting glucose values per week are <80 mg/dL, decrease the dose by 2 units immediately 1, 2

• If hypoglycemia occurs without clear cause, reduce the dose by 10-20% 1, 2

Recognizing When Basal Insulin Alone Is Insufficient

Signs of Overbasalization

• When basal insulin exceeds 0.5 units/kg/day, stop escalating and consider adding prandial insulin or a GLP-1 receptor agonist instead 1, 2

• Clinical signals of overbasalization include: bedtime-to-morning glucose differential ≥50 mg/dL, hypoglycemia (aware or unaware), and high glucose variability 1, 2

• If fasting glucose reaches target (80-130 mg/dL) but A1C remains above goal after 3-6 months, add prandial insulin rather than continuing to increase basal insulin 1, 2

Adjunctive Therapy Considerations

Metformin as Foundation

• Continue metformin when initiating or intensifying insulin therapy unless contraindicated (eGFR <30 mL/min/1.73 m²) 1, 2

• Metformin is the first-line agent and should remain part of the regimen even when adding basal insulin 1

Alternative to Prandial Insulin

• Consider adding a GLP-1 receptor agonist to basal insulin if postprandial hyperglycemia persists, as this minimizes hypoglycemia and weight gain risks compared to prandial insulin 1, 2

Special Clinical Situations

Steroid-Induced Hyperglycemia

• For patients on corticosteroids with bedtime hyperglycemia, NPH insulin given in the morning may be more appropriate than bedtime dosing, as steroids cause peak hyperglycemia 7-9 hours after administration 1

• For dexamethasone-induced hyperglycemia, use NPH insulin twice daily (2/3 of total dose in morning, 1/3 in early evening) at 0.3 units/kg/day total 1

Hospitalized Patients

• For hospitalized insulin-naive patients, start with 0.3-0.5 units/kg/day total daily dose, giving half as basal insulin 2

• For patients on high-dose home insulin (≥0.6 units/kg/day), reduce total daily dose by 20% upon hospitalization to prevent hypoglycemia 2

Common Pitfalls to Avoid

• Never delay insulin initiation in patients not achieving glycemic goals with oral medications—this constitutes therapeutic inertia and worsens outcomes 1, 2

• Do not continue escalating basal insulin beyond 0.5-1.0 units/kg/day without addressing postprandial hyperglycemia, as this leads to suboptimal control and increased hypoglycemia risk 1, 2

• Avoid using premixed insulin at bedtime in hospital settings due to unacceptably high rates of iatrogenic hypoglycemia 2

• Do not use sulfonylureas for steroid-induced hyperglycemia, as they are ineffective in this scenario 1