What to do when Lantus (insulin glargine) and Humalog (insulin lispro) are not effectively lowering blood sugar?

Managing Ineffective Insulin Therapy with Lantus and Humalog

When Lantus (insulin glargine) and Humalog (insulin lispro) are not effectively lowering blood sugar, you should intensify the insulin regimen by either adjusting the current doses, adding a GLP-1 receptor agonist, or advancing to a more complex insulin regimen based on the patient's specific glycemic patterns.

Assessment of Current Insulin Regimen

• Evaluate the adequacy of the basal insulin dose at every visit, looking for clinical signs of overbasalization such as elevated bedtime-to-morning glucose differentials, hypoglycemia, or high glucose variability 1
• Check if the patient is consistently taking insulin at the same time each day, as insulin glargine should be administered at a consistent time to maintain stable blood glucose levels 2
• Review for potential drug interactions that may decrease insulin effectiveness, including corticosteroids, diuretics, thyroid hormones, and sympathomimetic agents 3
• Assess for proper injection technique and insulin storage, as improper administration can reduce effectiveness 2

Step 1: Optimize Basal Insulin (Lantus)

• If fasting blood glucose remains elevated, increase the Lantus dose by 2 units every 3 days until reaching the fasting glucose target without hypoglycemia 1
• For patients requiring high doses of insulin (>0.5 units/kg/day) with A1C still above target, consider advancing to combination injectable therapy 2
• Consider switching to a concentrated formulation (U-300 glargine) for patients requiring larger doses, which offers longer duration of action than standard formulations 2

Step 2: Optimize Prandial Insulin (Humalog)

• If postprandial glucose levels remain elevated despite optimized basal insulin:
  • Adjust the Humalog dose by 1-2 units or 10-15% based on postprandial glucose patterns 1
  • Ensure Humalog is being administered immediately before meals 1
  • Consider adding additional mealtime doses if only using Humalog with one meal 1

Step 3: Consider Advanced Options

If optimizing the current regimen fails:

Option A: Add a GLP-1 Receptor Agonist

• Consider adding a GLP-1 receptor agonist to the insulin regimen, which can improve glycemic control without increasing hypoglycemia risk 1
• This combination has potent glucose-lowering actions with less weight gain and hypoglycemia compared to intensified insulin regimens 1
• Fixed-ratio combination products containing basal insulin plus a GLP-1 RA are available (insulin glargine plus lixisenatide or insulin degludec plus liraglutide) 1

Option B: Advance to a More Complex Insulin Regimen

• Progress to a full basal-bolus plan with prandial insulin at each meal if needed 1
• Consider self-mixed/split insulin plans or twice-daily premixed insulin if appropriate 1
• For patients on basal insulin with A1C still above target, add stepwise doses of prandial insulin, usually starting with one dose at the largest meal 1

Special Considerations

• When adding prandial insulin doses, particularly with the evening meal, consider decreasing the basal insulin dose to prevent nocturnal hypoglycemia 2
• Monitor for hypoglycemia when intensifying therapy; if hypoglycemia occurs without a clear reason, lower the corresponding insulin dose by 10-20% 1
• Insulin glargine provides more stable glycemic control with fewer episodes of nocturnal hypoglycemia compared to NPH insulin 4
• Patient education and self-management are crucial; consider referral to diabetes self-management education and support (DSMES) 1

Common Pitfalls to Avoid

• Therapeutic inertia: Delaying treatment intensification when glycemic targets are not met 1
• Failing to adjust mealtime insulin when long-acting insulin is held or reduced 2
• Not considering medication interactions that may affect insulin effectiveness 3
• Overlooking the importance of consistent timing of insulin administration 2
• Ignoring weight gain associated with insulin therapy, which can contribute to insulin resistance 3