What adjustments are needed for a patient with hypoglycemia on glipizide, insulin glargine, and Steglatro (ertugliflozin)?

Immediate Regimen Adjustment for Morning Hypoglycemia

Discontinue glipizide immediately and reduce insulin glargine by 20% to approximately 22 units at bedtime, while continuing Steglatro 5 mg unchanged. 1, 2

Rationale for Each Medication Adjustment

Glipizide (Sulfonylurea) - DISCONTINUE

• Glipizide carries a moderate to high risk of hypoglycemia and should be taken at the time of the main meal or discontinued entirely when fasting blood glucose values are consistently 60-80 mg/dL 3
• Older generation sulfonylureas like glipizide are particularly problematic in patients already experiencing hypoglycemia, as they continue stimulating insulin secretion regardless of glucose levels 3
• The combination of glipizide with basal insulin significantly increases hypoglycemia risk, with studies showing 4-6 times higher rates compared to insulin alone 3

Insulin Glargine (Lantus) - REDUCE BY 20%

• For recurrent fasting hypoglycemia (blood glucose 60-80 mg/dL), reduce the Lantus dose by 20%, bringing the dose from 28 units to approximately 22 units 1
• A 20% reduction is appropriate rather than 10% because the patient has recurrent (not isolated) morning hypoglycemia with values consistently below the target range of 80-130 mg/dL 1, 4
• The FDA label for insulin glargine specifically warns that hypoglycemia is the most common adverse reaction and requires dose adjustment when it occurs 4
• Meta-analysis data confirm that insulin glargine has lower hypoglycemia risk than NPH insulin, but dose reduction remains essential when hypoglycemia occurs 5

Steglatro (Ertugliflozin) - CONTINUE UNCHANGED

• SGLT2 inhibitors like Steglatro have a low intrinsic risk of hypoglycemia and do not require dose adjustment for hypoglycemia 3
• The FDA label explicitly states that when SGLT2 inhibitors are combined with insulin or insulin secretagogues, "a lower dose of insulin or insulin secretagogue may be required," but does not recommend adjusting the SGLT2 inhibitor itself 2
• Continue Steglatro at 5 mg daily as it provides cardiovascular and renal benefits independent of glucose-lowering effects 3

Monitoring Protocol After Adjustment

Immediate Monitoring (First Week)

• Check fasting blood glucose daily upon waking for at least one week 1
• For nocturnal hypoglycemia assessment, check blood glucose at bedtime, 3:00 AM, and upon waking for several days 1, 6
• Target fasting glucose range of 80-130 mg/dL 1, 4

Subsequent Titration Rules

• If more than 50% of fasting glucose values remain above 130 mg/dL after one week, increase insulin glargine by 2 units 1
• If two or more fasting glucose values per week fall below 80 mg/dL, decrease insulin glargine by an additional 2 units 1
• Make adjustments every 3 days during active titration 1

Critical Pitfalls to Avoid

Do Not Continue Current Regimen

• Continuing the same dose without adjustment after hypoglycemic events significantly increases risk of recurrent severe hypoglycemia 1
• The combination of sulfonylurea plus basal insulin in a patient with documented hypoglycemia is particularly dangerous and must be addressed immediately 3, 2

Do Not Reduce All Three Medications Proportionally

• SGLT2 inhibitors do not contribute to hypoglycemia and should not be reduced 3, 2
• The primary culprits are glipizide (which should be stopped) and excessive basal insulin (which should be reduced by 20%) 1, 2

Ensure Glucagon Availability

• All patients on basal insulin should have glucagon available for emergency use 1
• Educate the patient on hypoglycemia symptoms and treatment with 15-20 grams of fast-acting carbohydrates 7

Alternative Considerations if Hypoglycemia Persists

Timing Adjustment

• Consider changing insulin glargine administration from bedtime to morning to reduce nocturnal hypoglycemia risk while maintaining 24-hour coverage 1, 8
• Studies show equivalent glycemic control and hypoglycemia rates with morning versus bedtime administration of insulin glargine 8

Switch to Ultra-Long-Acting Insulin

• If hypoglycemia continues despite dose reduction, consider switching to insulin degludec (U-200) or insulin glargine U-300, which have lower nocturnal hypoglycemia rates than insulin glargine U-100 1
• These newer basal analogs provide more stable insulin levels over 24 hours 3

Follow-Up Timeline

• Schedule reassessment within 1-2 weeks to review glucose logs, identify patterns, and make further adjustments as needed 1, 6
• If basal insulin dose exceeds 0.5-1.0 units/kg/day after titration, consider whether the patient has developed overbasalization requiring addition of prandial insulin rather than further basal insulin escalation 1