What is a recommended regimen for duo therapy with insulin lispro (Humalog) and insulin glargine (Lantus)?

Recommended Duo Therapy Regimen with Insulin Lispro and Insulin Glargine

For duo therapy with insulin lispro (Humalog) and insulin glargine (Lantus), administer insulin glargine once daily at the same time each day for basal coverage, and add insulin lispro before the largest meal (typically dinner) starting at 4 units or 10% of the basal insulin dose, then titrate both insulins based on glucose monitoring. 1

Initiating the Regimen

Starting Insulin Glargine (Lantus)

• For insulin-naive patients with type 2 diabetes: Start with 10 units once daily or 0.1-0.2 units/kg/day 2, 3
• For patients with type 1 diabetes: Glargine should comprise approximately one-third of total daily insulin requirements, with the remainder covered by rapid-acting insulin 3
• Administer at a consistent time each day to maintain stable blood glucose levels—the specific time (morning, evening, or bedtime) matters less than consistency 2, 3

Adding Insulin Lispro (Humalog)

• Start with a single injection before the largest meal or the meal with the greatest postprandial glucose excursion 1
• Initial dose: 4 units or 10% of the basal insulin amount is a safe starting point 1
• This approach is simpler than multiple daily injections and allows gradual intensification based on patient response 1

Titration Strategy

Adjusting Insulin Glargine

• Titrate based on fasting blood glucose readings with a target of <120 mg/dL (6.7 mmol/L) 1, 2
• If basal insulin dose exceeds 0.5 units/kg/day and A1C remains above target, consider advancing to more intensive therapy rather than continuing to increase glargine alone 2, 4

Adjusting Insulin Lispro

• Titrate based on pre-meal and 2-hour postprandial glucose readings at the meal where lispro is administered 1, 4
• Target postprandial glucose <180 mg/dL (10.0 mmol/l) 5
• As prandial insulin doses increase significantly (particularly with evening meals), consider decreasing basal insulin to avoid overlapping insulin action and hypoglycemia risk 1, 2

Dosing Considerations for Type 2 Diabetes

• Total daily insulin requirements typically range from 0.4 to 1.0 units/kg/day, with patients with type 2 diabetes generally requiring higher doses (≥1 unit/kg) due to greater insulin resistance 1, 2
• Patients with type 2 diabetes have lower rates of hypoglycemia compared to type 1 diabetes, allowing for more aggressive titration 1

When to Intensify Beyond Duo Therapy

If A1C remains above target despite optimized duo therapy, consider these options:

• Add lispro before additional meals (typically breakfast and lunch next) to create a full basal-bolus regimen 1
• Add a GLP-1 receptor agonist instead of additional prandial insulin—this combination has potent glucose-lowering effects with less weight gain and hypoglycemia compared to multiple daily insulin injections 1, 6
• Switch to premixed insulin formulations (such as 70/30 or lispro mix 75/25) twice daily, though this offers less flexibility than separate basal-bolus dosing 1, 5

Critical Monitoring Parameters

• Self-monitored blood glucose: Check fasting glucose (for glargine titration) and pre-meal/postprandial glucose at the meal where lispro is given 1, 2
• A1C every 2-3 months to assess overall glycemic control 4
• Hypoglycemia awareness: While type 2 diabetes patients have lower hypoglycemia risk, monitor for symptoms especially as doses increase 1

Important Caveats and Pitfalls

• Continue metformin therapy when initiating this insulin regimen—it improves insulin sensitivity and should not be discontinued 1, 4
• Do not mix or dilute insulin glargine with any other insulin or solution due to its low pH formulation 2, 3
• Rotate injection sites within the same region (abdomen, thigh, or deltoid) to reduce lipodystrophy risk 3
• Administer insulin lispro immediately before meals (within 15 minutes) due to its rapid onset of action, unlike regular insulin which requires 30-45 minute lead time 7
• Research shows that adding prandial insulin lispro to basal glargine provides superior postprandial glucose control compared to basal insulin alone, with studies demonstrating HbA1c reductions of 0.75-1.0% when properly titrated 5, 8

Alternative Evidence-Based Approach

• Some evidence supports starting with premixed insulin lispro formulations (such as lispro mix 75/25 or 50/50) twice daily rather than separate basal-prandial therapy, which may achieve greater HbA1c reductions (-1.30% vs -1.08%) but with slightly higher hypoglycemia rates 5, 8
• However, separate basal-prandial therapy offers greater flexibility for dose adjustments and meal timing, making it preferable for most patients starting insulin intensification 1