What long-acting daytime insulin can be used with nighttime glargine (insulin glargine) at bedtime?

From the Guidelines

Detemir (insulin detemir) is not the most appropriate long-acting daytime insulin to use alongside nighttime glargine, as it has been removed from the market. Instead, consider using degludec, which is a long-acting basal analog that may convey a lower hypoglycemia risk compared with U-100 glargine when used in combination with oral agents 1. This combination provides 24-hour basal insulin coverage through complementary pharmacokinetic profiles. Typically, degludec would be administered in the morning while glargine is given at bedtime. Degludec has a duration of action of more than 42 hours, making it suitable for daytime coverage, while glargine provides steady coverage for 20-24 hours, ideal for overnight control. This split-basal regimen may be particularly beneficial for patients who experience dawn phenomenon or those who have inconsistent glycemic control with a single daily basal insulin. Dosing should be individualized based on blood glucose monitoring, with typical starting doses of 0.1-0.2 units/kg for each insulin, adjusted according to glucose patterns. Patients should be educated about monitoring for hypoglycemia and the importance of consistent meal timing when using this dual basal insulin approach. Some key points to consider when using this regimen include:

• Starting doses can be estimated based on body weight and the degree of hyperglycemia, with individualized titration over days to weeks as needed 1.
• Clinical signals that may prompt evaluation of overbasalization include basal dose greater than 0.5 units/kg, high bedtime-to-morning or postprandial-to-preprandial glucose differential, hypoglycemia, and high variability 1.
• Consideration of cost is an important component of effective management, and human insulin may be a more affordable option for some patients 1.

From the FDA Drug Label

Insulin Degludec Administered at Any Time Each Day as an Add-on to One or Two of the Following Oral Agents: Metformin, Sulfonylurea, or Pioglitazone in Adult Patients The efficacy of Insulin Degludec was evaluated in a 26-week randomized, open-label, multicenter trial in 447 patients with type 2 diabetes mellitus inadequately controlled on one or more oral antidiabetic agent (OADs) at baseline.

• Long-acting daytime insulin: Insulin Degludec can be used as a long-acting daytime insulin.
• Nighttime glargine at bedtime: There is no direct information in the provided drug labels that supports the use of a specific long-acting daytime insulin with nighttime glargine at bedtime. However, based on the information provided, Insulin Degludec can be considered as a long-acting insulin option, but its use with nighttime glargine at bedtime is not directly supported by the provided drug labels 2.

From the Research

Long-Acting Daytime Insulin Options

To manage blood glucose levels during the day when using nighttime glargine at bedtime, several long-acting insulin options can be considered. The choice of insulin depends on various factors including the patient's type of diabetes, lifestyle, and individual response to different insulins.

• Degludec: This ultralong-acting insulin analogue has been shown to improve glucose control in type 1 diabetes when switched from twice-daily glargine or detemir 3. Its flat and reproducible pharmacodynamic profile makes it a suitable option for daytime use.
• Detemir: Although primarily used as a basal insulin, detemir can be considered for daytime use, especially in patients who require a more flexible dosing regimen. However, studies suggest that detemir may require higher total daily basal insulin doses compared to glargine 4.
• Glargine: While glargine is commonly used at bedtime, it can also be administered in the morning as part of a flexible regimen, especially when combined with other oral medications like glimepiride 5. This approach can provide similar glycemic control and hypoglycemia risk as bedtime administration.

Considerations for Insulin Choice

When selecting a long-acting daytime insulin to use with nighttime glargine, several factors should be considered:

• Duration of action: The insulin should provide adequate coverage throughout the day without causing hypoglycemia.
• Flexibility: The ability to administer insulin at different times of the day can be beneficial for patients with varying schedules.
• Hypoglycemia risk: Insulins with a lower risk of hypoglycemia, such as degludec, may be preferred for daytime use.
• Dosing regimen: The simplicity of the dosing regimen and the need for multiple injections per day should be considered.

Glycemic Control and Safety

Studies have demonstrated that long-acting insulins like glargine and detemir can provide effective glycemic control and safety profiles when used appropriately 6, 7, 4. However, individual patient responses may vary, and careful monitoring of blood glucose levels and adjustment of insulin doses are necessary to achieve optimal control.