What adjustments should be made to a type 2 diabetes patient's medication regimen, currently on Humalog 75-25 (insulin lispro protamine/insulin lispro) 23 units daily and recently switched from Lantus (insulin glargine) to Jardiance (empagliflozin), due to nocturnal hypoglycemia?

Immediate Medication Adjustments for Nocturnal Hypoglycemia

Reduce the Humalog 75-25 dose by 20% immediately (from 23 units to approximately 18 units daily) and continue Jardiance, as recurrent nocturnal hypoglycemia with 4 episodes in one week requires urgent dose reduction to prevent dangerous hypoglycemic events. 1

Understanding the Problem

Your patient is experiencing recurrent nocturnal hypoglycemia (blood sugars in the 50s at night) despite already stopping Lantus. The issue is that Humalog 75-25 contains 75% insulin lispro protamine (an intermediate-acting basal component similar to NPH) that provides basal coverage for approximately 12-18 hours, which is likely causing the overnight lows. 2

The premixed insulin formulation means the patient is still receiving substantial basal insulin coverage from the protamine component, even though you discontinued the Lantus. 3

Step-by-Step Management Algorithm

Immediate Actions (Within 24 Hours)

• Reduce Humalog 75-25 by 20%: Decrease from 23 units to 18 units daily, as the American Diabetes Association recommends a 10-20% dose reduction for any hypoglycemic event without clear reversible cause, and with 4 episodes in one week, use the 20% reduction. 1

• Check blood glucose at bedtime, 3:00 AM, and upon waking for the next 3-7 days to identify the exact timing and pattern of nocturnal hypoglycemia. 1

• Ensure glucagon is available at home for emergency use, as all patients on insulin therapy should have glucagon readily accessible. 1

Monitoring Requirements (First Week)

• Check fasting blood glucose daily with a target range of 80-130 mg/dL. 1

• If more than 50% of fasting glucose values remain above target after one week, increase the dose by 2 units. 1

• If two or more fasting glucose values per week fall below 80 mg/dL, decrease the dose by an additional 2 units. 1

Consider Timing Adjustment

• Consider changing the Humalog 75-25 administration time from evening to morning if nocturnal hypoglycemia persists, as this shifts the peak insulin action away from overnight hours while maintaining 24-hour coverage. 1

Alternative Insulin Regimen (If Hypoglycemia Persists)

If hypoglycemia continues despite dose reduction, consider discontinuing Humalog 75-25 entirely and replacing with rapid-acting insulin only at mealtimes (such as Humalog regular), as guidelines explicitly recommend against overlapping multiple basal insulin sources. 1

This approach would involve:

• Starting with 4 units of rapid-acting Humalog before the largest meal or using 10% of the previous total daily dose (approximately 2 units). 4
• Titrating prandial doses by 1-2 units every 3 days based on 2-hour postprandial glucose readings. 4
• The Ozempic (GLP-1 receptor agonist) would provide some glucose-lowering effect with minimal hypoglycemia risk, and Jardiance would provide additional glucose control through renal glucose excretion. 2, 5

Role of Jardiance in This Regimen

Jardiance (empagliflozin) was an appropriate substitution for Lantus because:

• SGLT-2 inhibitors like Jardiance have very low hypoglycemia risk when used without insulin or sulfonylureas. 5
• Jardiance can be used adjunctively with insulin to improve control and reduce insulin requirements, though potential side effects should be considered. 2
• The combination of basal insulin plus SGLT-2 inhibitor may improve control and reduce the amount of insulin needed. 2

Ozempic Considerations

• Continue Ozempic as it provides glucose-lowering with weight loss and minimal hypoglycemia risk, and the combination of basal insulin plus GLP-1 receptor agonist is associated with less hypoglycemia than insulin-only regimens. 2

• Temporarily stop Ozempic only during acute illness with volume depletion, as recommended by sick day medication guidance. 1

Assess for Hypoglycemia Unawareness

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

• More frequent monitoring
• Potentially less aggressive glycemic targets (consider HbA1c target of <8% rather than <7% if unawareness is present)
• 2-3 weeks of scrupulous avoidance of hypoglycemia to reverse unawareness 1

Common Pitfalls to Avoid

• Never continue premixed insulin at the same dose after multiple hypoglycemic episodes, as this dramatically increases the risk of severe hypoglycemia and potential hospitalization. 1

• Do not assume stopping Lantus alone is sufficient when the patient is still on Humalog 75-25, which contains a substantial basal insulin component (75% protamine lispro). 3

• Avoid using premixed insulin in complex regimens where precise basal-bolus separation is needed, as randomized trials show premixed insulin regimens have significantly increased hypoglycemia rates compared to basal-bolus therapy. 4

Alternative Long-Acting Basal Insulin Options

If you need to restart basal insulin in the future, 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 (Lantus). 1

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