Medically reviewed by Drugs.com. Last updated on Nov 9, 2020.
(IN soo lin N P H)
- Isophane Insulin
- NPH Insulin
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
HumuLIN N: 100 units/mL (3 mL, 10 mL) [contains metacresol, phenol]
NovoLIN N: 100 units/mL (10 mL) [contains metacresol, phenol]
NovoLIN N ReliOn: 100 units/mL (10 mL) [contains metacresol, phenol]
Suspension Pen-injector, Subcutaneous:
HumuLIN N KwikPen: 100 units/mL (3 mL) [contains metacresol, phenol]
NovoLIN N FlexPen: 100 units/mL (3 mL) [contains metacresol, phenol]
NovoLIN N FlexPen ReliOn: 100 units/mL (3 mL) [contains metacresol, phenol]
Brand Names: U.S.
- HumuLIN N KwikPen [OTC]
- HumuLIN N [OTC]
- NovoLIN N FlexPen ReliOn [OTC]
- NovoLIN N FlexPen [OTC]
- NovoLIN N ReliOn [OTC]
- NovoLIN N [OTC]
- Insulin, Intermediate-Acting
Insulin acts via specific membrane-bound receptors on target tissues to regulate metabolism of carbohydrate, protein, and fats. Target organs for insulin include the liver, skeletal muscle, and adipose tissue.
Within the liver, insulin stimulates hepatic glycogen synthesis. Insulin promotes hepatic synthesis of fatty acids, which are released into the circulation as lipoproteins. Skeletal muscle effects of insulin include increased protein synthesis and increased glycogen synthesis. Within adipose tissue, insulin stimulates the processing of circulating lipoproteins to provide free fatty acids, facilitating triglyceride synthesis and storage by adipocytes; also directly inhibits the hydrolysis of triglycerides. In addition, insulin stimulates the cellular uptake of amino acids and increases cellular permeability to several ions, including potassium, magnesium, and phosphate. By activating sodium-potassium ATPases, insulin promotes the intracellular movement of potassium.
Normally secreted by the pancreas, insulin products are manufactured for pharmacologic use through recombinant DNA technology using either E. coli or Saccharomyces cerevisiae. Insulins are categorized based on the onset, peak, and duration of effect (eg, rapid-, short-, intermediate-, and long-acting insulin). Insulin NPH, an isophane suspension of human insulin, is an intermediate-acting insulin.
Onset of Action
1 to 2 hours; Peak effect: 4 to 12 hours
Time to Peak
Plasma: 6 to 10 hours
Duration of Action
14 to 24 hours
Use: Labeled Indications
Diabetes mellitus, types 1 and 2, treatment: Treatment of types 1 and 2 diabetes mellitus to improve glycemic control in adults and pediatric patients.
Off Label Uses
Gestational diabetes mellitus
Based on the American College of Obstetricians and Gynecologists Practice Bulletin for the management of gestational diabetes mellitus (GDM) and the American Diabetes Association Standards of Medical Care for the management of diabetes in pregnancy, insulin may be used to treat GDM when nutrition and exercise therapy are not effective.
Hypersensitivity to insulin NPH or any component of the formulation; during periods of hypoglycemia
Documentation of allergenic cross-reactivity for drugs in this class is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Note: Insulin NPH is an intermediate-acting insulin formulation. Insulin requirements vary dramatically between patients and dictate frequent monitoring and close medical supervision.
Diabetes mellitus, type 1, treatment: SubQ:
Note: Insulin NPH must be used concomitantly with rapid- or short-acting insulins (ie, multiple daily injection regimen). The total daily doses (TDD) presented below are expressed as the total units/kg/day of all insulin formulations combined.
General insulin dosing:
Initial TDD: ~0.4 to 0.5 units/kg/day; conservative initial doses of 0.2 to 0.4 units/kg/day may be considered to avoid the potential for hypoglycemia; higher initial doses may be required in patients who are obese, sedentary, or presenting with ketoacidosis (AACE [Handelsman 2015]; ADA 2020).
Usual TDD maintenance range: 0.4 to 1 units/kg/day in divided doses (ADA 2020).
Division of TDD (multiple daily injections):
Basal insulin: Generally, 40% to 50% of the TDD is given as basal insulin (intermediate- or long-acting) (AACE [Handelsman 2015]; ADA 2019). Insulin NPH may be administered in 2 divided doses daily (either as equally divided doses, or as ~2/3 of the dose before the morning meal and ~1/3 of the dose before the evening meal or at bedtime). Alternatively, dividing insulin NPH into 3 or 4 doses per day may reduce hypoglycemic risk and establish more consistent basal insulin profile (Peters 2013).
Prandial insulin: The remaining portion (ie, 50% to 60%) of the TDD is then divided and administered before, at, or just after mealtimes depending on the formulation (eg, short-, rapid-, or ultra-rapid acting) (AACE [Handelsman 2015]; ADA 2020).
Dosage adjustment: Dosage must be titrated to achieve glucose control and avoid hypoglycemia. Adjust dose to maintain premeal and bedtime glucose in target range. 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. To minimize hypoglycemia risk, basal insulins are generally titrated once or twice weekly (eg, every 3 or 7 days) (ADA 2019; McCall 2012).
Diabetes mellitus, type 2, treatment: SubQ:
Note: May be initiated in patients with severe or symptomatic hyperglycemia (eg, HbA1c ≥10%, blood glucose ≥300 mg/dL, presence of polyuria/polydipsia), or who have inadequate glycemic control on metformin ± other noninsulin agents (ADA 2020). Consider a dose reduction (eg, by 50%) or discontinuation of insulin secretagogues (sulfonylureas, meglitinides) when initiating insulin therapy (ADA/EASD [Davies 2018]). Use of long-acting basal analogs may be preferred over insulin NPH if minimization of hypoglycemia is a primary concern (AACE/ACE [Garber 2020]; ADA 2020).
Initial: 0.1 to 0.2 units/kg/day or 10 units/day administered as a single dose (usually at bedtime) or in 2 divided doses (ADA 2020; Lipska 2017). If HbA1c >8% prior to initiation of basal insulin, 0.2 to 0.3 units/kg/day is recommended (AACE/ACE [Garber 2020]).
For elevated fasting plasma glucose: Adjust dose using evidence-based titration algorithm (eg, by 2 units every 3 days) while avoiding hypoglycemia (AACE/ACE [Garber 2020]; ADA 2020).
For elevated HbA1c despite achieving fasting plasma glucose target:
Patients using once daily insulin NPH (eg, at bedtime): Consider switching to a twice daily regimen by administering ~80% of the current bedtime dose in 2 divided doses (one example division would be 2/3 of the dose in the morning and 1/3 of the dose at bedtime) (ADA 2020).
Patients using twice daily insulin NPH: Consider intensification of therapy with additional agents that target postprandial glucose rather than continuing to increase the insulin NPH dose (AACE/ACE [Garber 2020]; ADA 2020).
For hypoglycemia: If no clear reason for hypoglycemia, decrease dose by 10% to 20% (ADA 2020); for severe hypoglycemia (ie, requiring assistance from another person or blood glucose <40 mg/dL) reduce dose by 20% to 40% (AACE/ACE [Garber 2020]).
Dosage adjustment when adding prandial insulin: Consider reducing the basal insulin dose by 4 units (or ~10%) if HbA1c is <8% when initiating prandial insulin (ADA 2020).
Patients with diabetes receiving enteral feedings (ADA 2020): Note: TDD of insulin is divided into a basal component (intermediate- or long-acting insulin) and nutritional and correctional components (regular insulin or rapid-acting insulins).
Basal component: SubQ: Continue previous basal insulin dose or administer 30% to 50% of TDD as insulin NPH; if basal insulin naive, administer insulin NPH 5 units every 12 hours.
Patients with diabetes undergoing surgery: SubQ: On the evening before surgery or procedure, reduce the usual dose by 25%; on the morning of surgery or procedure, reduce the usual dose by 25% to 50% (ADA 2020; Pichardo-Lowden 2012).
Conversion from long-acting insulin analogs to insulin NPH: Consider initiating insulin NPH at 80% (eg, 20% reduction) of previous basal insulin total daily dose; administer as a single dose (usually at bedtime) or in 2 divided doses (ADA 2020; Lipska 2017).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Refer to adult dosing.
Insulin NPH is an intermediate-acting insulin formulation which is usually administered subcutaneously once or twice daily. When compared to insulin regular, insulin NPH has a slower onset and longer duration of activity. Insulin doses should be individualized based on patient needs; adjustments may be necessary with changes in physical activity, meal patterns, acute illness, or with changes in renal or hepatic function. Insulin requirements vary dramatically between patients and dictate frequent monitoring and close medical supervision. Insulin regimens vary widely by region, practice, and institution; consult institution-specific guidelines.
Type 1 diabetes mellitus: Children and Adolescents: Note: For basal insulin coverage, long-acting insulin analogs are preferred over insulin NPH due to decreased risk of hypoglycemia (AACE/ACE [Handelsman 2015]; ADA 2018; ADA [Chiang 2014]). The daily doses presented are expressed as the total units/kg/day of all insulin formulations combined.
Initial total daily insulin: SubQ:Initial: 0.4 to 0.5 units/kg/day in divided doses (AACE/ACE [Handelsman 2015]; ADA 2018); usual range: 0.4 to 1 units/kg/day in divided doses (AACE/ACE [Handelsman 2015; ADA 2018; Silverstein 2005); lower doses (0.25 units/kg/day) may be used especially in young children to avoid potential hypoglycemia (Beck 2015); higher doses may be necessary for some patients (eg, obese, concomitant steroids, puberty, sedentary lifestyle, following diabetic ketoacidosis presentation) (AACE/ACE [Handelsman 2015]; ADA 2018)
Usual total daily maintenance range: SubQ: Doses must be individualized; however, an estimate can be determined based on phase of diabetes and level of maturity (ISPAD [Danne 2018]; ISPAD [Sundberg 2017]):
Partial remission phase (Honeymoon phase): <0.5 units/kg/day
Prepubertal children (not in partial remission):
Infants ≥6 months and Children ≤6 years: 0.4 to 0.8 units/kg/day
Children ≥7 years: 0.7 to 1 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
Division of daily insulin requirement (multiple daily injections):
Basal insulin: Generally, ~30% to 50% of the total daily insulin is given as basal insulin (intermediate- or long-acting) (AACE/ACE [Handelsman 2015]; ADA 2018; ISPAD [Danne 2018]; Peters 2013). When utilizing a twice daily NPH regimen, ~50% to 60% of the total daily insulin administered as NPH has been recommended with more (~2/3) of the total daily insulin administered in the morning and less (~1/3) of the total daily dose administered in the evening or at bedtime (ISPAD [Danne 2014]). Dividing the total daily dose of insulin NPH into 3 or 4 doses per day may reduce hypoglycemic risk and establish a more consistent basal insulin profile (Peters 2013).
Prandial insulin: The remaining portion of the total daily dose is then divided and administered before or at mealtimes (depending on the formulation) as rapid-acting (eg, aspart, glulisine, lispro) or short-acting (regular). In most type 1 patients, the use of a rapid-acting insulin analog is preferred over regular insulin to reduce hypoglycemia risk (AACE/ACE [Handelsman 2015]; ADA 2018; ADA [Chiang 2014]; ISPAD [Danne 2018]).
Dose titration: Treatment and monitoring regimens must be individualized to maintain premeal and bedtime glucose in target range, titrate dose 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.
Patients receiving enteral/parenteral feedings: Data is limited in pediatric patients; in adults, the following is recommended: Bolus or continuous enteral feedings: SubQ: Continue previous basal insulin dose or if basal insulin naive, administer 30% to 50% of total daily dose of insulin received while being fed as insulin NPH (ADA 2018); administer in conjunction with nutritional and correctional insulin dosing with a rapid-acting or regular insulin.
Surgical patients (ISPAD [Jefferies 2018]): Note: Diabetic patients should be scheduled as the first case of the day.
Morning procedure: Administer 50% to 70% of the usual morning dose of insulin NPH OR administer IV insulin (regular) infusion; begin IV fluids containing dextrose; in general rapid acting insulin should be omitted until after surgery and patient is able to eat unless it is needed to correct significant hyperglycemia and/or significant ketone (>0.1 mmol/mol) production is present.
Afternoon procedure: Administer 70% to 100% of the usual morning dose of insulin NPH depending on the amount of breakfast allowed.
Postprocedure: Once normal oral intake is achieved, resume usual insulin regimen; monitor closely due to risk of changes related to surgery (postoperative stress, medication changes, inactivity)
Major surgeries: Omit morning insulin (short and long acting) and start IV insulin (regular) infusion and IV dextrose; patients on continuous subcutaneous insulin infusion should discontinue CSII when IV insulin infusion is started; once normal oral intake is resumed, then resume usual insulin regimen; monitor closely due to risk of changes related to surgery (postoperative stress, medication changes, inactivity)
Type 2 diabetes mellitus: Limited data available: Note: The goal of therapy is to achieve an HbA1c <7% as quickly as possible using the safe titration of medications. Initial therapy in metabolically unstable patients (eg, plasma glucose ≥250 mg/dL, HbA1c >9% and symptoms excluding acidosis) may include once daily intermediate-acting insulin or basal insulin in combination with lifestyle changes and metformin. In patients who fail to achieve glycemic goals with metformin and basal insulin, may consider initiating prandial insulin (regular insulin or rapid acting insulin) and titrate to achieve goals. Once initial goal reached, insulin should be slowly tapered over 2 to 6 weeks by decreasing the insulin dose by 10% to 30% every few days and the patient transitioned to lowest effective doses or metformin monotherapy if able (AAP [Copeland 2013]; ADA 2018; ISPAD [Zeitler 2018]).
Children ≥10 years and Adolescents with ketosis/ketoacidosis/ketonuria: SubQ: Initial: 0.25 to 0.5 units/kg/dose once daily; use in in combination with lifestyle changes and metformin to achieve goals (ISPAD [Zeitler 2018])
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
SubQ: For subcutaneous administration into the thigh, upper arm, buttocks, or abdomen; do not administer IM or IV, or in an insulin pump. Absorption rates vary amongst injection sites; be consistent with area used while rotating injection sites within the same region to reduce the risk of lipodystrophy or localized cutaneous amyloidosis. Rotating from an injection site where lipodystrophy/cutaneous amyloidosis is present to an unaffected site may increase risk of hypoglycemia.
In order to properly resuspend the insulin, vials should be carefully inverted or rolled at least 10 times, Humulin N KwikPen should be rolled between the palms ten times and inverted 180° ten times, and Novolin N FlexPen should be inverted 180° twenty times prior to the first injection and ten times thereafter. Cartridges [Canadian product] should be inverted 180° at least ten times. Properly resuspended insulin NPH 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, or if white particles are stuck to the bottom or wall of the container. Cold injections should be avoided.
Per the manufacturer labeling, Humulin N from a vial may be mixed with insulin lispro or insulin regular and Novolin N from a vial may be mixed only with insulin regular. When mixing insulin NPH with other insulins in a syringe, insulin NPH should be drawn into the syringe after the other insulin preparations. Do not dilute or mix other insulin formulations with insulin NPH contained in a cartridge [Canadian product] or prefilled pen. When there are less than 12 units remaining in Novolin N FlexPen, replace it with a new one to ensure even mixing.
For prefilled pens, prime the needle before each injection with 2 units of insulin. Once injected, hold the needle in the skin for a count of 5 (Humulin N KwikPen) or 6 (Novolin N FlexPen) after the dose dial has returned to 0 units before removing the needle to ensure the full dose has been administered.
Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.
Humulin N vials: Store unopened vials in refrigerator between 2°C and 8°C (36°F to 46°F; do not freeze; keep away from heat and sunlight. Once punctured (in use), vials may be stored for up to 31 days in the refrigerator between 2°C and 8°C (36°F to 46°F) or at room temperature ≤30°C (≤86°F)
Humulin N KwikPen: Store unopened in the refrigerator between 2°C and 8°C (36°F to 46°F); do not freeze; keep away from heat and sunlight. Once punctured (in use), should be stored below 30°C (86°F) for up to 14 days.
Novolin N vials: Store unopened vials in refrigerator between 2°C and 8°C (36°F to 46°F) until product expiration date or at room temperature ≤25°C (≤77°F) for up to 42 days; do not freeze; keep away from heat and sunlight. Once punctured (in use), store vials at room temperature ≤25°C (≤77°F) for up to 42 days; refrigeration of in-use vials is not recommended.
Novolin N FlexPen: Store unopened pen in the refrigerator between 2°C and 8°C (36°F to 46°F) until product expiration date or at room temperature <30°C (<86°F) for 28 days; do not freeze; keep away from heat and sunlight. Once punctured (in use), store <30°C (<86°F) for up to 28 days; refrigeration of in-use pens is not recommended.
Canadian products: Unopened vials, cartridges, and pens should be stored under refrigeration between 2°C and 8°C (36°F to 46°F) until the expiration date; do not freeze; keep away from heat and sunlight. Once punctured (in use), Humulin vials, cartridges and pens should be stored at room temperature <25°C (<77°F) for up to 4 weeks. Once punctured (in use), Novolin ge vials, cartridges, and pens may be stored for up to 1 month at room temperature <25°C (<77°F) for vials or <30°C (<86°F) for pens/cartridges; do not refrigerate.
Alpha-Glucosidase Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with an alpha-glucosidase inhibitor and monitor patients for hypoglycemia. Consider therapy modification
Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy
Androgens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy
Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy
Beta-Blockers: May enhance the hypoglycemic effect of Insulins. Monitor therapy
Dipeptidyl Peptidase-IV Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Consider therapy modification
Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy
Edetate CALCIUM Disodium: May enhance the hypoglycemic effect of Insulins. Monitor therapy
Glucagon-Like Peptide-1 Agonists: May enhance the hypoglycemic effect of Insulins. Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Consider therapy modification
Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy
Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy
Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy
Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Monitor therapy
Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy
Liraglutide: May enhance the hypoglycemic effect of Insulins. Management: Consider reducing the liraglutide dose if coadministered with insulin. Prescribing information for the Saxenda brand of liraglutide recommends a dose decrease of 50%. Monitor blood glucose for hypoglycemia. Consider therapy modification
Macimorelin: Insulins may diminish the diagnostic effect of Macimorelin. Avoid combination
Maitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy
Metreleptin: May enhance the hypoglycemic effect of Insulins. Management: Insulin dosage adjustments (including potentially large decreases) may be required to minimize the risk for hypoglycemia with concurrent use of metreleptin. Monitor closely for signs and symptoms of hypoglycemia. Consider therapy modification
Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy
Pegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy
Pioglitazone: May enhance the adverse/toxic effect of Insulins. Specifically, the risk for hypoglycemia, fluid retention, and heart failure may be increased with this combination. Management: If insulin is combined with pioglitazone, consider insulin dose reductions to avoid hypoglycemia. Monitor patients for fluid retention and signs/symptoms of heart failure, and consider pioglitazone dose reduction or discontinuation if heart failure occurs Consider therapy modification
Pramlintide: May enhance the hypoglycemic effect of Insulins. Management: Upon initiation of pramlintide, decrease mealtime insulin dose by 50% to reduce the risk of hypoglycemia. Monitor blood glucose frequently and individualize further insulin dose adjustments based on glycemic control. Consider therapy modification
Prothionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy
Quinolones: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy
Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy
Rosiglitazone: Insulins may enhance the adverse/toxic effect of Rosiglitazone. Specifically, the risk of fluid retention, heart failure, and hypoglycemia may be increased with this combination. Avoid combination
Salicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy
Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor and monitor patients for hypoglycemia. Consider therapy modification
Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined:
Cardiovascular: Peripheral edema
Dermatologic: Injection site pruritus
Endocrine & metabolic: Amyloidosis (cutaneous at injection site), hypoglycemia, hypokalemia, lipodystrophy, lipohypertrophy, weight gain
Hypersensitivity: Anaphylaxis, hypersensitivity reaction
Local: Atrophy at injection site, erythema at injection site, hypertrophy at injection site, injection site reaction, swelling at injection site
Neuromuscular & skeletal: Swelling of extremities
Ophthalmic: Visual disturbance
Concerns related to adverse effects:
• Glycemic control: Hyper- or hypoglycemia may result from changes in insulin strength, manufacturer, type, and/or administration method. The most common adverse effect of insulin is hypoglycemia. The timing of hypoglycemia differs among various insulin formulations. Hypoglycemia may result from changes in meal pattern (eg, macronutrient content, timing of meals), changes in the level of physical activity, increased work or exercise without eating, or changes to coadministered medications. Use of long-acting insulin preparations (eg, insulin degludec, insulin detemir, insulin glargine) may delay recovery from hypoglycemia. Patients with renal or hepatic impairment may be at a higher risk. Symptoms differ in patients and may change over time in the same patient; awareness may be less pronounced in those with long-standing diabetes, diabetic nerve disease, patients taking beta-blockers, or in those who experience recurrent hypoglycemia. Profound and prolonged episodes of hypoglycemia may result in convulsions, unconsciousness, temporary or permanent brain damage, or even death. Insulin requirements may be altered during illness, emotional disturbances, or other stressors. Instruct patients to use caution with ethanol; may increase risk of hypoglycemia. In clinical trials insulin NPH has been associated with a modestly increased risk of hypoglycemia (including nocturnal hypoglycemia) compared with long-acting analogs (Lipska 2017; Rosenstock 2005; Rys 2015; Singh 2009). However, an observational study in patients with type 2 diabetes from a large health care delivery system found no difference in the incidence of ER visits or hospitalization for hypoglycemia with NPH compared with glargine/detemir when treating to conventional targets in a real world setting (Lipska 2018).
• Hypersensitivity: Hypersensitivity reactions (serious, life-threatening and anaphylaxis) have occurred. If hypersensitivity reactions occur, discontinue administration and initiate supportive care measures.
• Hypokalemia: Insulin (especially IV insulin) causes a shift of potassium from the extracellular space to the intracellular space, possibly producing hypokalemia. If left untreated, hypokalemia may result in respiratory paralysis, ventricular arrhythmia and even death. Use with caution in patients at risk for hypokalemia (eg, loop diuretic use). Monitor serum potassium and supplement potassium when necessary.
• Bariatric surgery:
– Type 2 diabetes, hypoglycemia: Closely monitor insulin dose requirement throughout active weight loss with a goal of eliminating antidiabetic therapy or transitioning to agents without hypoglycemic potential; hypoglycemia after gastric bypass, sleeve gastrectomy, and gastric band may occur (Mechanick 2013). Insulin secretion and sensitivity may be partially or completely restored after these procedures (Korner 2009; Peterli 2012). Rates and timing of type 2 diabetes improvement and resolution vary widely by patient. Insulin dose reduction of ≥75% has been suggested after gastric bypass for patients without severe β-cell failure (fasting c-peptide <0.3 nmol/L) (Cruijsen 2014). Avoid the use of bolus insulin injections or dose conservatively with close clinical monitoring in the early phases after surgery.
– Weight gain: Insulin therapy is preferred if antidiabetic therapy is required during the perioperative period (Mechanick 2019). Evaluate risk versus benefit of long-term postoperative use and consider alternative therapy due to potential for insulin-induced weight gain (Apovian 2015).
• Cardiac disease: Concurrent use with peroxisome proliferator-activated receptor (PPAR)-gamma agonists, including thiazolidinediones (TZDs) may cause dose-related fluid retention and lead to or exacerbate heart failure, particularly when used in combination with insulin. If PPAR-gamma agonists are prescribed, monitor for signs and symptoms of heart failure. If heart failure develops, consider PPAR-gamma agonist dosage reduction or therapy discontinuation.
• Hepatic impairment: Use with caution in patients with hepatic impairment. Dosage requirements may be reduced.
• Renal impairment: Use with caution in patients with renal impairment. Dosage requirements may be reduced.
• Hospitalized patients with diabetes: Exclusive use of a sliding scale insulin regimen (insulin regular) in the inpatient hospital setting is strongly discouraged. In the critical care setting, continuous IV insulin infusion (insulin regular) has been shown to best achieve glycemic targets. In noncritically ill patients with either poor oral intake or taking nothing by mouth, basal insulin or basal plus bolus is preferred. In noncritically ill patients with adequate nutritional intake, a combination of basal insulin, nutritional, and correction components is preferred. An effective insulin regimen will achieve the goal glucose range without the risk of severe hypoglycemia). A blood glucose value <70 mg/dL should prompt a treatment regimen review and change, if necessary, to prevent further hypoglycemia (ADA 2020).
Dosage form specific issues:
• Multiple dose injection pens: According to the Centers for Disease Control and Prevention (CDC), pen-shaped injection devices should never be used for more than one person (even when the needle is changed) because of the risk of infection. The injection device should be clearly labeled with individual patient information to ensure that the correct pen is used (CDC, 2012).
• Administration: Insulin NPH is NOT intended for IV or IM administration.
• Patient education: Diabetes self-management education (DSME) is essential to maximize the effectiveness of therapy.
Diabetes mellitus: Plasma glucose (typically before meals and snacks and at bedtime; occasionally additional monitoring may be required), electrolytes, HbA1c (at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; quarterly in patients not meeting treatment goals or with therapy change [ADA 2020]); renal function, hepatic function, weight.
Gestational diabetes mellitus: Blood glucose 4 times daily (1 fasting and 3 postprandial) until well controlled, then as appropriate (ACOG 190 2018).
Poorly controlled diabetes during pregnancy can be associated with an increased risk of adverse maternal and fetal outcomes, including diabetic ketoacidosis, preeclampsia, spontaneous abortion, preterm delivery, delivery complications, major birth defects, stillbirth, and macrosomia (ACOG 201 2018). To prevent adverse outcomes, prior to conception and throughout pregnancy, maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2020; Blumer 2013).
Due to pregnancy-induced physiologic changes, insulin requirements tend to increase as pregnancy progresses, requiring frequent monitoring and dosage adjustments. Following delivery, insulin requirements decrease rapidly (ACOG 201 2018; ADA 2020).
Insulin is the preferred treatment of type 1 and type 2 diabetes mellitus in pregnancy, as well as gestational diabetes mellitus, when pharmacologic therapy is needed (ACOG 190 2018; ACOG 201 2018; ADA 2020). NPH insulin may be used to treat diabetes mellitus in pregnancy (ACOG 190 2018; ACOG 201 2018; Blumer 2013)
What is this drug used for?
• It is used to lower blood sugar in patients with high blood sugar (diabetes).
All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
• Injection site irritation
• Weight gain
WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
• Low blood sugar like dizziness, headache, fatigue, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating.
• Low potassium like muscle pain or weakness, muscle cramps, or an abnormal heartbeat.
• Vision changes
• Burning or numbness feeling
• Severe dizziness
• Passing out
• Mood changes
• Slurred speech
• Swelling of arms or legs
• Injection site thick skin, pits, or lumps
• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.
Frequently asked questions
- Can Trulicity be used with insulin?
- How and where should I inject insulin?
- How long can Humulin be unrefrigerated?
- How long does Humulin last?
- Is Humulin fast or long-acting insulin?
More about insulin isophane
- Drug Information
- Insulin human isophane (nph) Subcutaneous (Advanced Reading)
- Insulin NPH (InnoLets, Pens, and PenFill Cartridges)
- Insulin NPH (Vials)
Related treatment guides
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.