At what time of day in relation to meals are Regular (insulin) and NPH (Neutral Protamine Hagedorn) insulin typically administered?

From the Guidelines

Regular insulin and NPH insulin are typically administered at different times in relation to meals, with Regular insulin taken 30 minutes before meals and NPH insulin administered twice daily, once before breakfast and once before dinner or at bedtime, as supported by the most recent guidelines 1. The administration timing is crucial due to the distinct onset and duration profiles of these insulins.

• Regular insulin has a faster onset of action, typically within 30 minutes, and peaks 2-3 hours after injection, making it suitable for managing post-meal blood glucose elevations.
• NPH insulin, on the other hand, has a delayed onset of 2-4 hours and peaks 4-10 hours after injection, making it more suitable for providing background insulin between meals and overnight. When using both insulins together, they are often mixed in the same syringe and administered before breakfast and dinner, aiming to mimic natural insulin patterns, with Regular insulin handling immediate meal-related glucose rises and NPH providing background insulin between meals and overnight, as indicated in the guidelines 1. Key points to consider include:
• The total NPH dose is typically divided, with 2/3 given before breakfast and 1/3 given before dinner, as recommended in the 2023 standards of care in diabetes 1.
• The timing and dosing of Regular and NPH insulin can be adjusted based on individual patient needs and blood glucose levels, emphasizing the importance of personalized care and ongoing monitoring 1.

From the FDA Drug Label

In one non-blinded clinical study (Study A, n=409), adult patients with type 1 diabetes were randomized to treatment with either LEVEMIR at 12-hour intervals, LEVEMIR morning and bedtime or NPH human insulin morning and bedtime. In a randomized, controlled clinical study (Study C, n=749), patients with type 1 diabetes were treated with once-daily (bedtime) LEVEMIR or NPH human insulin, both in combination with human soluble insulin before each meal for 6 months. Type 2 Diabetes – Adult In a 24-week, non-blinded, randomized, clinical study (Study E, n=476), LEVEMIR administered twice-daily (before breakfast and evening) was compared to a similar regimen of NPH human insulin as part of a regimen of combination therapy with one or two of the following oral antidiabetes agents (metformin, insulin secretagogue, or α–glucosidase inhibitor)

Regular and NPH insulin administration times in relation to meals are as follows:

• NPH human insulin: typically administered morning and bedtime 2, or before breakfast and evening 2
• Regular insulin: although not directly mentioned in the provided text, it is typically administered before meals It is essential to note that the administration times may vary depending on the specific patient's needs and the treating physician's recommendations.

From the Research

Administration Timing of Regular and NPH Insulin

• Regular insulin is typically administered 30 to 45 minutes before a meal 3.
• However, in practice, patients often inject regular insulin closer to mealtime, which can cause higher post-prandial serum glucose levels and increase the potential for hypoglycemia in the postabsorptive period 3.
• NPH insulin can be administered at different times of the day, including morning and bedtime, with bedtime administration resulting in improved basal glycaemia and overall metabolic control in patients with Type 2 diabetes 4.
• The time interval between injection of regular insulin and food intake has a minimal influence on blood glucose control in type 1 diabetic patients on a basal-bolus insulin scheme 5.
• Regular insulin can be injected either 5 minutes or 30 minutes before each of the three main meals, with no significant difference in daily insulin dosages or glucose profiles 5.

Meal-Related Administration

• Regular insulin is often administered before meals to control post-prandial glucose surges 3, 5.
• NPH insulin can be administered in combination with regular insulin, with the NPH insulin providing a basal insulin level and the regular insulin controlling post-prandial glucose surges 3, 6.
• The administration of NPH insulin at bedtime can help improve overnight glycemic control in children and adolescents with IDDM 6.

Comparison with Other Insulin Types

• Insulin Glargine, a long-acting insulin analog, is typically administered as a single daily dose, often at nighttime, and does not treat post-prandial hyperglycemia, requiring supplementation with short-acting insulin at mealtimes 7.
• NPH insulin can be used to achieve constant basal insulin levels, especially when given in multiple overlapping doses together with short-acting insulin at mealtimes, although this may be less convenient and more costly than using Insulin Glargine 7.