What are the recent updates in insulin therapy for patients with diabetes?

Recent Updates in Insulin Therapy

The most significant recent advances in insulin therapy include FDA-approved automated insulin delivery (AID) systems for type 1 diabetes, ultra-rapid-acting insulin formulations (faster-acting insulin aspart and ultra-rapid lispro), and second-generation ultra-long-acting basal analogs (insulin degludec and glargine U-300) that reduce hypoglycemia risk while maintaining glycemic control. 1

Automated Insulin Delivery Systems

Hybrid closed-loop (automated insulin delivery) systems are now the preferred insulin delivery method for patients with type 1 diabetes who can safely use them. 1

• The FDA has approved multiple AID systems that automatically adjust basal insulin delivery based on continuous glucose monitoring data 1
• AID systems demonstrate superior glycemic control compared to sensor-augmented pump therapy alone, with increased time-in-range and reduced hypoglycemia over 3-month periods 1
• Real-world studies confirm safety and effectiveness in both adolescents and adults with type 1 diabetes 1
• These systems should be considered whenever feasible for individuals with type 1 diabetes, either independently or with caregiver assistance 1

Ultra-Rapid-Acting Insulin Formulations

Two new ultra-rapid-acting analog (URAA) formulations provide faster absorption and earlier peak activity than traditional rapid-acting analogs. 1

• Faster-acting insulin aspart and ultra-rapid insulin lispro (Lyumjev) reduce postprandial glucose excursions more effectively than standard rapid-acting analogs 1
• Lyumjev can be administered at the start of a meal or within 20 minutes after starting a meal, offering greater dosing flexibility 2
• These formulations have accelerated absorption profiles designed to provide more insulin activity in the first portion of their action curve 1

Second-Generation Ultra-Long-Acting Basal Insulins

Insulin degludec and glargine U-300 represent major advances in basal insulin therapy with ultra-long duration of action exceeding 24 hours. 1

Insulin Degludec

• Degludec forms soluble multihexamers in subcutaneous tissue, creating a depot that provides stable, peakless glucose-lowering for over 24 hours 3, 4
• Demonstrates lower within-person variability in absorption compared to first-generation basal insulins 5
• Can be administered at flexible times each day (alternating 8-40 hour intervals between doses) while maintaining non-inferior glycemic control to glargine U-100 3
• Reduces nocturnal hypoglycemia risk compared to glargine U-100 in type 1 diabetes 1
• Available in both U-100 and U-200 concentrations 3

Glargine U-300 (Toujeo)

• Has a longer duration of action than glargine U-100 (Lantus), with glucose-lowering activity exceeding 24 hours and a flatter, more prolonged pharmacokinetic profile 6
• Requires approximately 10-18% higher daily doses compared to glargine U-100 to achieve equivalent glycemic control due to modestly lower per-unit efficacy 6
• Provides reduced injection volume for patients requiring large insulin doses, potentially improving comfort and adherence 6
• Confers lower hypoglycemia risk compared to glargine U-100 in type 1 diabetes 1

Inhaled Insulin

Inhaled human insulin offers a non-injectable prandial option with rapid peak and shortened duration of action. 1

• Has faster peak and shorter duration than rapid-acting analogs 1
• May cause less hypoglycemia and weight gain compared to injectable rapid-acting analogs 1
• Available only in fixed doses (4-, 8-, and 12-unit cartridges), limiting dose titration flexibility 1

Continuous Glucose Monitoring Integration

CGM use is now considered standard of care for most people with type 1 diabetes using insulin therapy. 1

• Automatic insulin suspension at preset glucose levels reduces nocturnal hypoglycemia in pump users 1
• Integration with insulin pumps enables the automated insulin delivery systems described above 1

Concentrated Insulin Formulations

Multiple concentrated insulin preparations reduce injection volume for patients requiring high insulin doses. 1

• U-300 glargine and U-200 degludec provide higher basal insulin doses per volume 1, 3
• U-200 insulin lispro (rapid-acting) reduces injection volume and may improve adherence 1, 2
• U-500 regular insulin (5 times concentrated) has both prandial and basal properties, indicated for patients requiring >200 units daily 1
• All concentrated insulins are available only in prefilled pens to minimize dosing errors 1

Insulin Analogs vs. Human Insulin

In type 1 diabetes, analog insulins demonstrate clear advantages over human insulins. 1

• Associated with less hypoglycemia and weight gain compared to NPH and regular human insulin 1
• Achieve equivalent or lower A1C levels 1
• Basal analogs provide flatter, more constant plasma concentrations than NPH insulin 1
• Rapid-acting analogs have quicker onset, earlier peak, and shorter duration than regular human insulin 1

Cost and Access Considerations

The introduction of interchangeable biosimilars and unbranded analog versions represents an important recent development for insulin access. 1

• Current and upcoming price reductions require reassessment of insulin-taking behavior and treatment plans 1
• Clinicians should review insulin choice accounting for cost factors at regular 3-6 month intervals 1
• Despite analog advantages, expense may be prohibitive for some patients, and human insulins remain viable options 1

Key Clinical Pitfalls

• Never transfer glargine U-300 or degludec U-200 from pens to syringes—this causes severe overdosage and life-threatening hypoglycemia 1
• Concentrated insulins require careful patient education about proper pen use 1
• When switching between insulin formulations or concentrations, close medical supervision with increased glucose monitoring frequency is essential 2
• Lipohypertrophy from repeated injections at the same site distorts insulin absorption—rotate injection sites within the same region 1, 2
• Use 4-mm pen needles as first-line choice to avoid intramuscular injection, which can cause severe hypoglycemia especially with long-acting insulins 7