When should NPH (Neutral Protamine Hagedorn) insulin be administered and how long does it provide glycemic control?

From the Guidelines

NPH insulin should be administered at bedtime to provide effective glycemic control, with the option to add a morning dose based on individual patient needs and glucose monitoring results, as evidenced by the most recent guidelines 1. When initiating NPH insulin, the starting dose can be estimated based on body weight (0.1-0.2 units/kg/day) and the degree of hyperglycemia, with individualized titration over days to weeks as needed 1.

Key Considerations for NPH Insulin Administration

• The principal action of basal insulin, such as NPH, is to restrain hepatic glucose production and limit hyperglycemia overnight and between meals 1.
• NPH insulin begins working within 1-2 hours after injection, reaches its peak effect in 4-8 hours, and provides glycemic control for approximately 12-18 hours total.
• Some patients may require additional rapid-acting insulin at mealtimes for optimal control.
• The cloudy appearance of NPH insulin requires gentle mixing by rolling the vial or pen between the palms before injection to ensure proper suspension of the insulin particles.

Titration and Monitoring

• Choose an evidence-based titration algorithm, such as increasing the dose by 2 units every 3 days to reach the FPG goal without hypoglycemia 1.
• Assess the adequacy of the insulin dose at every visit and consider clinical signals to evaluate for overbasalization and the need for adjunctive therapies.
• Clinical signals that may prompt evaluation of overbasalization include basal dose greater than 0.5 units/kg, high bedtime-morning or post-prandial-to-preprandial glucose differential, hypoglycemia, and high glucose variability 1.

Special Considerations

• Long-acting basal analogs (U-100 glargine or detemir) have been demonstrated to reduce the risk of symptomatic and nocturnal hypoglycemia compared with NPH insulin 1.
• Longer-acting basal analogs (U-300 glargine or degludec) may convey a lower hypoglycemia risk compared with U-100 glargine when used in combination with oral agents 1.
• Clinicians should be aware of the potential for overbasalization with insulin therapy and adjust the treatment plan accordingly 1.

From the FDA Drug Label

CLINICAL STUDIES The efficacy and safety of LEVEMIR given once-daily at bedtime or twice-daily (before breakfast and at bedtime, before breakfast and with the evening meal, or at 12-hour intervals) was compared to that of once-daily or twice-daily NPH human insulin or once-daily insulin glargine in non-blinded, randomized, parallel studies of 6004 patients with diabetes (3724 with type 1, and 2280 with type 2). 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. LEVEMIR-treated patients had a decrease in HbA1c similar to that of NPH human insulin

The NPH insulin should be administered morning and bedtime or at 12-hour intervals. The duration of glycemic control provided by NPH insulin is not explicitly stated in the provided drug label, therefore no conclusion can be drawn. 2

From the Research

Administration Timing of NPH Insulin

• NPH insulin can be administered at bedtime to improve basal glycaemia and overall metabolic control in patients with Type 2 diabetes and overt fasting hyperglycaemia 3.
• Bedtime administration of NPH insulin results in increased basal insulinaemia, leading to improved basal glycaemia compared to morning insulin administration 3.

Duration of Glycemic Control

• The duration of glycemic control provided by NPH insulin is not explicitly stated in the provided studies, but it is known to be an intermediate-acting insulin.
• A study comparing NPH insulin with human ultralente insulin found that NPH insulin provided similar overall glycemic control, but with higher blood glucose levels before the bedtime snack 4.
• Another study found that NPH insulin and neutral protamine lispro (NPL) were equally effective in controlling overnight glycemia 5.

Comparison with Other Insulin Regimens

• A study comparing evening and night glycemic control with different insulin regimens found that reducing the evening premeal lispro dose by 20% and increasing the bedtime basal NPH dose by 25% resulted in lower postprandial blood glucose concentrations, but no difference in nighttime or prebreakfast glucose concentrations 6.
• A study comparing bedtime injections of insulin glargine and NPH insulin found that insulin glargine was more effective in reducing fasting blood glucose levels and had a lower incidence of nocturnal hypoglycemic events 7.