Insulin NPH and Insulin Regular

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, suspension:

HumuLIN 70/30: Insulin NPH suspension 70% [intermediate acting] and insulin regular solution 30% [short acting]: 100 units/mL (3 mL, 10 mL) [vial]

HumuLIN 70/30 KwikPen: Insulin NPH suspension 70% [intermediate acting] and insulin regular solution 30% [short acting]: 100 units/mL (3 mL)

NovoLIN 70/30: Insulin NPH suspension 70% [intermediate acting] and insulin regular solution 30% [short acting]: 100 units/mL (10 mL) [vial]

• HumuLIN 70/30
• HumuLIN 70/30 KwikPen
• NovoLIN 70/30

0.5 hours; Peak effect: 2-12 hours

Time to Peak

Based on individual components:

Insulin regular: 0.8-2 hours

Insulin NPH: 6-10 hours

Hypersensitivity to any component of the formulation; during episodes of hypoglycemia

Note: Insulin NPH is an intermediate-acting insulin and regular insulin is a short-acting insulin administered by SubQ injection. When compared to insulin NPH, the combination product (insulin NPH and insulin regular) has a shorter onset of action and a similar duration of action. With combination insulin products, the proportion of short-acting to long-acting insulin is fixed; basal vs prandial dose adjustments cannot be made. Fixed-ratio insulins (such as insulin NPH and insulin regular combination) are typically administered as 2 daily doses with each dose intended to cover two meals and a snack. Because of variability in the peak effect and individual patient variability in activities, meals, etc, it may be more difficult to achieve complete glycemic control using fixed combinations of insulins; frequent monitoring and close medical supervision may be necessary.

Diabetes mellitus, type 1:

General insulin dosing:

Type 1: Note: Multiple daily doses are utilized and guided by blood glucose monitoring. Combinations of different insulin formulations are commonly used. The daily doses presented below are expressed as the total units/kg/day of all insulin formulations combined. Insulin NPH and insulin regular combination product is not intended for initial therapy; basal insulin requirements should be established first to direct dosing of combination insulin products.

Usual maintenance range: SubQ: 0.5 to 1 units/kg/day in divided doses. An estimate of anticipated needs may be based on body weight and/or activity factors as follows:

Nonobese: 0.4 to 0.6 units/kg/day

Obese: 0.8 to 1.2 units/kg/day

Pubescent Children and Adolescents: During puberty, requirements may substantially increase to >1 unit/kg/day and in some cases up to 2 units/kg/day (IDF-ISPAD 2011).

Division of daily insulin requirement ("conventional therapy"): Generally, 50% to 75% of the total daily dose (TDD) is given as an intermediate-acting (eg, NPH) or a long-acting form of insulin (in 1 to 2 daily injections). The remaining portion of the TDD is then divided and administered before or at mealtimes (depending on the formulation) as a rapid-acting or short-acting form of insulin.

Adjustment of dose: Dosage must be titrated to achieve glucose control and avoid hypoglycemia. Since combinations of agents are frequently used, dosage adjustment must address the individual component of the insulin regimen which most directly influences the blood glucose value in question, based on the known onset and duration of the insulin component. Treatment and monitoring regimens must be individualized. Also see Additional Information or Pharmacotherapy Pearls.

Diabetes mellitus, type 2: SubQ:

General considerations for insulin use in type 2 diabetes:

Timing of initiation: The goal of therapy is to achieve an HbA1c <7%. According to a position statement by the ADA and European Association for the Study of Diabetes (EASD), dual therapy (metformin + a second antihyperglycemic agent) is recommended in patients with type 2 diabetes who fail to achieve glycemic goals after ~3 months with lifestyle interventions and metformin monotherapy (unless contraindications to metformin exist). Preference is not given for adding insulin or a noninsulin agent as the second antihyperglycemic agent (drug choice should be individualized based on patient characteristics). However, insulin should be considered as part of a combination regimen when hyperglycemia is severe, particularly if patient is symptomatic or has catabolic features (eg, weight loss, ketosis). If insulin is selected, the addition of basal insulin with a long-acting insulin (ie, glargine or detemir [not insulin NPH and insulin regular combination]) is recommended. If HbA1c target not achieved after ~3 months of dual therapy, may proceed to triple therapy (Inzucchi 2015).

Intensification of therapy: If HbA1c target has not been met, despite titrating basal insulin (ie, long-acting insulin) to provide acceptable fasting blood glucose concentrations, intensification of therapy should be considered to cover postprandial glucose excursions. Options include adding a mealtime insulin (1 to 3 injections of a rapid-acting insulin analog [lispro, aspart, glulisine]) or adding a GLP-1 receptor agonist (eg, exenatide, liraglutide). Alternatively, although less studied, may transition from basal insulin (ie, long-acting insulin) to a twice daily premixed (or biphasic) insulin analog (70/30 aspart mix, 75/25 or 50/50 lispro mix) (Inzucchi 2015).

Refer to indication-specific dosing for obesity-related information (may not be available for all indications).

For SubQ administration:

Humulin 70/30: May be diluted with the universal diluent, Sterile Diluent for Humalog, Humulin N, Humulin R, Humulin 70/30, and Humulin R U-500. Do not dilute insulin contained in a cartridge or prefilled pen.

Novolin 70/30: Insulin Diluting Medium for NovoLog is not intended for use with Novolin 70/30 or any insulin product other than insulin aspart.

SubQ administration: For subcutaneous administration into the thigh, upper arm, buttocks, or abdomen; do not administer IM or IV, or in an insulin pump. Rotate injection sites within the same region to reduce the risk of lipodystrophy. In order to properly resuspend the insulin, vials should be carefully rolled several times, prefilled pens should be rolled between the palms ten times and inverted 180° ten times, and cartridges [Canadian product] should be inverted 180° at least ten times. Properly resuspended insulin should look uniformly cloudy or milky; do not use if any white insulin substance remains at the bottom of the container, if any clumps are present, if the insulin remains clear after adequate mixing, or if white particles are stuck to the bottom or wall of the container. Cold injections should be avoided. Insulin NPH and insulin regular combination products should be administered 30 to 45 minutes before a meal; typically given once or twice daily. Do not mix insulin NPH and insulin regular (combination product) with any other insulin formulation or diluents. Combination insulin products are not recommended for use in an external SubQ insulin infusion pump.