Can glargine (insulin glargine) and degludec (insulin degludec) be used together for glucose control?

Using Insulin Glargine and Degludec Together for Glucose Control

Yes, insulin glargine and insulin degludec can be used together for glucose control in specific clinical scenarios, though this combination is not a first-line approach and should be reserved for patients with complex insulin requirements who have failed to achieve adequate control with standard insulin regimens.

When to Consider Combination Basal Insulin Therapy

The American Diabetes Association (ADA) guidelines provide a structured approach to insulin therapy that typically follows a progression:

1. First-line approach: Start with a single basal insulin (either glargine OR degludec) 1
2. If inadequate control: Add prandial insulin or GLP-1 receptor agonist 1
3. For complex cases: Consider combination injectable therapy 1

Indications for Combined Basal Insulins

• Patients with severe insulin resistance requiring large doses (>0.5 U/kg/day) of basal insulin 1
• Patients with persistent glycemic variability despite optimized single basal insulin therapy
• Patients with recurrent nocturnal hypoglycemia on a single basal insulin
• Patients with unpredictable daily schedules who might benefit from complementary pharmacokinetic profiles

Pharmacological Rationale

Insulin glargine and insulin degludec have different pharmacokinetic profiles:

• Insulin glargine: Forms microprecipitates after injection, providing 24-hour coverage
• Insulin degludec: Forms soluble multi-hexamers that slowly dissociate, providing ultra-long duration (>42 hours)

This combination may provide more stable glucose control due to:

1. Different absorption mechanisms reducing variability 2, 3
2. Complementary time-action profiles
3. Potentially lower risk of hypoglycemia compared to high doses of a single basal insulin

Implementation Strategy

When implementing combined basal insulin therapy:

1. Start with a single basal insulin titrated to maximum effective dose
2. Add the second basal insulin at a low dose (typically 10% of total daily insulin)
3. Administer at different times:
   • Glargine: typically in the evening
   • Degludec: typically in the morning
4. Monitor fasting glucose patterns over 3-7 days
5. Adjust doses based on glucose patterns:
   • Increase by 2-4 units every 3-7 days until target achieved 4
   • Total basal insulin should generally not exceed 50% of total daily insulin dose

Monitoring and Safety Considerations

• Increased hypoglycemia risk: Monitor closely, especially during initiation
• Cost considerations: Using two basal insulins increases treatment cost
• Patient education: Ensure proper understanding of the complex regimen
• Regular reassessment: Evaluate continued need for dual basal insulin therapy

Alternative Approaches to Consider First

Before combining basal insulins, consider these alternatives:

1. Optimize single basal insulin dosing and timing
2. Add a GLP-1 receptor agonist to basal insulin (preferred by ADA) 1
3. Progress to basal-bolus therapy with mealtime insulin 1
4. Consider fixed-ratio combinations of basal insulin with GLP-1 receptor agonists 1

Evidence on Combined Basal Insulins

While direct studies on combined glargine and degludec are limited, comparative studies show:

• Degludec demonstrates lower day-to-day variability compared to glargine 3, 5
• Glargine U-300 shows lower hypoglycemia risk compared to degludec in some studies 2
• Both insulins have demonstrated cardiovascular safety 6, 7

The complementary profiles suggest potential benefits in combination therapy for selected patients, though this approach should be reserved for those who have failed standard insulin regimens.