What adjustments should be made to a patient's diabetes medication regimen, currently consisting of Humalog (insulin lispro) 75-25, Ozempic (semaglutide) 1 mg, and Lantus (insulin glargine) at bedtime, who has experienced recurrent episodes of hypoglycemia with blood glucose levels dropping into the 50s four times over the past week?

Immediate Medication Adjustments for Recurrent Hypoglycemia

This patient requires immediate reduction of both Lantus and Humalog 75-25 doses by 20% due to recurrent severe hypoglycemia, with consideration for discontinuing the Humalog 75-25 entirely given the dangerous overlap of three insulin products. 1

Critical Problem: Excessive Insulin Overlap

This regimen contains three separate insulin products providing overlapping basal coverage, creating a dangerous situation:

• Humalog 75-25 contains 75% intermediate-acting insulin (similar to NPH) + 25% rapid-acting insulin 2
• Lantus provides 24-hour basal coverage 3
• Ozempic enhances insulin secretion and delays gastric emptying 3

The combination of Humalog 75-25 and Lantus creates redundant basal insulin coverage that is not supported by clinical guidelines and significantly increases hypoglycemia risk. 4 This overlap is particularly dangerous because both insulins are providing basal coverage simultaneously throughout the day. 4

Immediate Dose Adjustments

For Severe Recurrent Hypoglycemia (4 episodes in one week):

Reduce Lantus by 20% immediately - for any hypoglycemic event without clear reversible cause, a 10-20% reduction is indicated, and with 4 episodes in one week, use the 20% reduction. 1

Reduce Humalog 75-25 by 20% immediately - the premixed insulin contains intermediate-acting insulin that contributes to basal coverage and likely overlaps dangerously with Lantus. 1, 2

Consider discontinuing Humalog 75-25 entirely and replacing with rapid-acting insulin only (Humalog or lispro) at mealtimes, as guidelines explicitly recommend against overlapping two different basal insulins. 4

Monitoring Protocol After Dose Reduction

• Check blood glucose at bedtime, 3:00 AM, and upon waking for several days to identify nocturnal hypoglycemia patterns 1
• Check fasting blood glucose daily for at least one week 1
• Target fasting glucose range: 80-130 mg/dL 1
• Ensure glucagon is available - all patients on basal insulin should have glucagon for emergency use 1, 5

Subsequent Titration After Initial Reduction

• If more than 50% of fasting glucose values remain above target after one week, increase by 2 units 1
• If two or more fasting glucose values per week fall below 80 mg/dL, decrease by an additional 2 units 1
• Make adjustments every 3 days during active titration 1

Special Considerations for This Regimen

Timing Adjustment:

Consider changing Lantus administration from bedtime to morning to reduce nocturnal hypoglycemia risk while maintaining 24-hour coverage. 1 This is particularly important given the 4 episodes of hypoglycemia in the 50s.

Ozempic Interaction:

Ozempic (semaglutide) increases hypoglycemia risk when combined with insulin by enhancing insulin secretion and delaying gastric emptying. 3 The dose of 1 mg weekly is the maximum dose, which may be contributing to the hypoglycemia when combined with excessive insulin.

Sick Day Management:

During acute illness with volume depletion, temporarily stop Ozempic and reduce insulin doses as recommended by sick day medication guidance. 5 Patients should seek assistance if they cannot keep up with fluid intake or have recurrent low blood glucose readings. 5

Recommended Simplified Regimen

Strongly consider transitioning to:

• Lantus once daily (reduced by 20% from current dose initially) 1
• Rapid-acting insulin (Humalog/lispro) only at mealtimes - starting with 4 units before the largest meal 4
• Continue Ozempic 1 mg weekly (or consider reducing to 0.5 mg if hypoglycemia persists) 3
• Discontinue Humalog 75-25 to eliminate the dangerous basal insulin overlap 4

This approach eliminates the redundant basal coverage from Humalog 75-25 while maintaining appropriate mealtime coverage. 4

Critical Threshold Monitoring

Watch for signs of overbasalization if Lantus dose exceeds 0.5 units/kg/day, including: 1

• High bedtime-to-morning glucose differential (≥50 mg/dL)
• Hypoglycemia episodes
• High glucose variability

Alternative Insulin Options

If hypoglycemia persists despite dose reduction, consider switching to newer ultra-long-acting basal analogs such as insulin degludec (Tresiba) or U-300 glargine (Toujeo), which have lower nocturnal hypoglycemia rates than U-100 glargine. 1

Hypoglycemia Unawareness Assessment

Evaluate whether the patient has developed hypoglycemia unawareness, which requires: 5

• More frequent monitoring
• Potentially less aggressive glycemic targets
• 2-3 weeks of scrupulous avoidance of hypoglycemia to reverse unawareness 5, 6

Recurrent hypoglycemia causes both defective glucose counterregulation and hypoglycemia unawareness through a vicious cycle. 6 Short-term avoidance of hypoglycemia reverses hypoglycemia unawareness in most affected patients. 6

Follow-Up Timing

Schedule reassessment within 1-2 weeks after dose reduction to review glucose logs, identify patterns, and make further adjustments as needed. 1

Common Pitfalls to Avoid

• Never continue the same dose without adjustment after hypoglycemic events - this significantly increases risk of recurrent severe hypoglycemia 1
• Never routinely overlap two different basal insulins (Humalog 75-25's intermediate component + Lantus) - this creates unnecessary complexity with increased hypoglycemia risk 4
• Never delay addressing recurrent hypoglycemia - 4 episodes in one week represents a medical emergency requiring immediate intervention 5