What are the options for weekly insulin therapy, such as insulin glargine (insulin glargine) or insulin degludec (insulin degludec), for patients requiring insulin therapy?

Weekly Insulin Options for Patients Requiring Insulin Therapy

Currently available weekly insulin options include insulin icodec, which has demonstrated similar or better glycemic control compared to daily basal insulins with a comparable safety profile in patients with type 2 diabetes. 1, 2, 3

Available Weekly Insulin Options

• Insulin icodec is the most advanced once-weekly insulin currently in development, with phase 3 trials showing efficacy and safety comparable to daily basal insulins 2
• Insulin icodec has a half-life of approximately 196 hours (>1 week), allowing for once-weekly administration 2
• Recent meta-analysis of ONWARDS phase 3 trials showed insulin icodec achieved greater HbA1c reduction (mean difference -0.17%) compared to daily basal insulins 3
• Higher proportions of patients achieved HbA1c <7% with insulin icodec compared to daily insulins 3

Daily Basal Insulin Options (For Comparison)

• Insulin degludec is an ultra-long-acting daily insulin with a half-life >25 hours, providing stable glucose-lowering effects throughout the 24-hour period 4
• Insulin glargine (U-100 and U-300) is a long-acting insulin analog that can be administered once daily 5
• Insulin detemir is another long-acting analog that can be used once or twice daily depending on the patient's needs 6
• NPH insulin is a more affordable alternative but has a more pronounced peak and shorter duration than analog insulins, with higher risk of hypoglycemia 6

Efficacy Considerations

• In phase 3 trials, insulin icodec demonstrated better glucose control compared to both insulin glargine and insulin degludec in type 2 diabetes 2
• The DUAL VIII randomized controlled trial demonstrated greater durability of glycemic treatment effect with insulin degludec compared to insulin glargine 5, 6
• Insulin degludec provides similar long-term glycemic control to insulin glargine in insulin-naive patients with type 2 diabetes, with lower rates of nocturnal hypoglycemia 7
• Concentrated insulin formulations (U-200 degludec, U-300 glargine) may be beneficial for patients requiring large insulin doses 5

Safety Considerations

• Insulin icodec showed similar rates of hypoglycemia compared to insulin glargine in type 2 diabetes, although there was a higher hypoglycemic event rate with insulin icodec in type 1 diabetes 2
• Meta-analysis showed significantly higher incidence of level 1 hypoglycemia with insulin icodec but no significant difference in levels 2,3 and combined 2/3 hypoglycemia compared to daily insulins 3
• Insulin degludec has demonstrated lower rates of nocturnal hypoglycemia compared to insulin glargine 7
• Long-acting insulin analogs (degludec, glargine U-300) have a modestly lower absolute risk for hypoglycemia compared with NPH insulin 5

Practical Implementation

• When initiating insulin therapy, metformin should be continued while sulfonylureas and DPP-4 inhibitors may be weaned or discontinued 5
• For insulin icodec, steady state is achieved after 3-4 weekly injections 2
• For insulin degludec, in adults, it can be injected subcutaneously once daily at any time of day, while in pediatric patients it should be injected at the same time every day 8
• When switching between insulin types, more frequent blood glucose monitoring is recommended during the transition period 6

Common Pitfalls to Avoid

• Inadequate monitoring during transition between insulin types can lead to poor glycemic control 6
• Assuming dose equivalence can lead to inadequate glycemic control, as individual responses vary and dose adjustments are often needed 6
• Overlooking injection timing differences between insulin types can lead to hypoglycemia 6
• Forgetting about half-life differences can lead to gaps in coverage when transitioning between insulin types 6

Future Developments

• Insulin icodec is the most advanced weekly insulin in development but is not yet FDA approved 2, 3
• The ONWARDS clinical trial program for insulin icodec consists of multiple phase 3 trials evaluating its efficacy and safety in various patient populations 3
• Weekly insulin administration may improve treatment adherence by reducing injection frequency by >85% compared to once-daily basal insulin analogs 2