Insulin NPH and Insulin Regular

Dosage Forms

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]

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

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

Pharmacology

Mechanism of Action

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) and insulin regular is an intermediate-acting combination insulin product with a more rapid onset than that of insulin NPH alone.

Pharmacokinetics/Pharmacodynamics

Excretion

Urine

Onset of Action

0.5 hours; Peak effect: 2 to 12 hours

Time to Peak

Based on individual components:

Insulin regular: 0.8 to 2 hours

Insulin NPH: 6 to 10 hours

Duration of Action

18 to 24 hours

Use: Labeled Indications

Diabetes mellitus, types 1 and 2: Treatment of types 1 and 2 diabetes mellitus to improve glycemic control

Use: Off Label

Gestational diabetes mellitus (GDM)yes

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 ACOG 190 2018, ADA 2019.

Contraindications

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

Dosage and Administration

Dosing: Adult

Note: Insulin NPH and insulin regular combination consists of an intermediate-acting insulin (NPH) and a short-acting insulin (regular). With combination insulin products, the proportion of short-acting to long-acting insulin is fixed; basal vs prandial dose adjustments cannot be made. 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.

Diabetes mellitus, type 1: SubQ:

General insulin dosing: Note: Use of premixed insulin is not generally recommended in type 1 diabetes. Most patients should be treated with multiple daily injections of prandial and basal insulin or continuous subcutaneous insulin infusion (CSII) (ADA 2019; Peters 2013). The total daily doses (TDD) presented below are expressed as the total units/kg/day of all insulin formulations combined.

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/ACE [Handelsman 2015]; ADA 2019).

Usual TDD maintenance range: 0.4 to 1 units/kg/day in divided doses (ADA 2019).

Dosage adjustment: Dosage must be titrated to achieve glucose control and avoid hypoglycemia. Note: If using insulin NPH and insulin regular combination, the TDD is typically divided into 2 doses. Given the fixed proportion of individual components in premixed insulin combination products, independent adjustment of the basal or prandial component is not possible. Therefore, use of premixed insulins should be reserved for patients unwilling to take more than two daily doses of insulin and unable to mix individual insulins. In these patients, consistent carbohydrate intake at each meal is essential (Peters 2013).

Diabetes mellitus, type 2: SubQ: Note: Initiation of premixed insulin is an option if adequate glycemic control has not been achieved with other injectable therapy including a GLP-1 receptor agonist and/or basal insulin (± prandial insulin) (ADA 2019).

Initial: If insulin naive, administer 0.3 units/kg/day or 10 to 12 units/day in 2 or 3 divided doses or if converting from other insulin therapy, administer the current total daily insulin dose in 2 or 3 divided doses (dose may require adjustment based on individual patient needs) (ADA 2019).

Dosage adjustment: Individualize dose adjustment based on type of biphasic insulin used; adjustment may be more complex with three-times-daily regimen. Risk of hypoglycemia is greater given the fixed proportion of individual components (ADA 2019).

In patients who develop hypoglycemia (without clear reason), dosage reductions of 10% to 20% have been recommended for basal and prandial insulins (as individual components); in cases of severe hypoglycemia (requiring assistance from another person or blood glucose <40 mg/dL) dosage reductions of 20% to 40% have been recommended (AACE/ACE [Garber 2019]; ADA 2019).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Insulin NPH is an intermediate-acting insulin and regular insulin is a short-acting insulin; the combination product is not intended for initial therapy; basal insulin requirements should be established first to direct dosing of the combination insulin products. 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. Premixed insulins are not recommended for routine use in pediatric patients; the proportion of short-acting to intermediate-acting insulin is fixed in the combination products; basal vs prandial dose adjustments cannot be made; premixed insulins may be useful when adherence is an issue (AACE/ACE [Handelsman 2015]; Beck 2015; ISPAD [Danne 2018]). Insulin regimens vary widely by region, practice, and institution; consult institution-specific guidelines.

Type 1 diabetes mellitus: Children and Adolescents: Note: Fixed ratio insulins (such as insulin NPH and insulin regular combination) are typically administered as 2 daily doses with each dose intended to cover 2 meals and a snack.

General insulin dosing: The daily doses presented are expressed as the total units/kg/day of all insulin formulations combined. Premixed insulin is not recommended for routine use in pediatric patients; may be useful when adherence is an issue (Beck 2015; ISPAD [Danne 2018]).

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 of anticipated needs may be 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

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. With combination insulin products, the proportion of rapid-acting to long-acting insulin is fixed; basal vs prandial dose adjustments cannot be made.

Type 2 diabetes mellitus: Children ≥10 years and Adolescents: SubQ: The goal of therapy is to achieve an HbA_1c <7% as quickly as possible using the safe titration of medications. Initial therapy in metabolically unstable patients (eg, plasma glucose ≥250 mg/dL, HbA_1c >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]). 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. Note: Patients who are ketotic or present with ketoacidosis require aggressive management as indicated.

Administration

SubQ administration: Insulin NPH and insulin regular combination products are administered by SubQ injection, typically in 2 divided doses/day with each dose intended to cover two meals or a meal and a snack; administer ~30 to 45 minutes before a meal. Administer into the thigh, upper arm, buttocks, or abdomen; 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 70/30 KwikPen should be rolled between the palms ten times and inverted 180° ten times, Novolin 70/30 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 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.

Do not administer IM or IV, or in an insulin pump. Do not mix with any other insulin formulation or diluents.

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 70/30 KwikPen) or 6 (Novolin 70/30 FlexPen) after the dose dial has returned to 0 units before removing the needle to ensure the full dose has been administered. When there are <12 units remaining in Novolin 70/30 FlexPen replace it with a new one to ensure even mixing.

Dietary Considerations

Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.

Storage

Humulin 70/30:

Vials: Store unopened vials in refrigerator between 2°C and 8°C (36°F to 46°F) or at room temperature below 30°C (86°F). If stored at room temperature, the vial must be discarded after 31 days. Do not freeze; discard if frozen. 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).

KwikPen: Store unopened pen in a refrigerator between 2°C and 8°C (36°F to 46°F) or at room temperature below 30°C (86°F); if stored at room temperature, then unopened pen must be discarded after 10 days. Do not freeze; discard if frozen. Keep away from heat and sunlight. Once punctured (in use), pen should be stored at room temperature below 30°C (86°F) for up to 10 days; do not refrigerate in-use pens.

Novolin 70/30:

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; discard if frozen. Keep away from heat and sunlight. Once punctured (in use), store vials at room temperature ≤25°C (≤77°F) for up to 42 days; do not refrigerate in-use vials.

FlexPen: Store unopened pens in 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 up to 28 days. Do not freeze; discard if frozen. Keep away from heat and sunlight. Once in use, store pens at room temperature ≤30°C (≤86°F) for up to 28 days; do not refrigerate in-use pens.

Canadian products: All 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; discard if frozen. 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.

Drug Interactions

Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. Monitor therapy

Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Beta-Blockers: May enhance the hypoglycemic effect of Insulins. Exceptions: Levobunolol; Metipranolol. 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. Exceptions: Liraglutide. 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: If liraglutide is used for the treatment of diabetes (Victoza), consider insulin dose reductions. The combination of liraglutide and insulin should be avoided if liraglutide is used exclusively for weight loss (Saxenda). Consider therapy modification

Macimorelin: Insulins may diminish the diagnostic effect of Macimorelin. Avoid combination

Maitake: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. 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. Consider therapy modification

Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. 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, dose reductions should be considered to reduce the risk of hypoglycemia. Monitor patients for fluid retention and signs/symptoms of heart failure. 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 Blood Glucose Lowering Agents. Monitor therapy

Quinolones: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolones may diminish the therapeutic effect of Blood Glucose Lowering Agents. 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 Blood Glucose Lowering Agents. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. 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

Adverse Reactions

See individual agents. Frequency not defined.

Cardiovascular: Peripheral edema

Dermatologic: Pruritus

Endocrine & metabolic: Hypoglycemia, hypokalemia, weight gain

Hypersensitivity: Hypersensitivity reaction

Immunologic: Immunogenicity

Local: Hypertrophy at injection site, lipoatrophy at injection site

Warnings/Precautions

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.
• 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.

Disease-related concerns:

• 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 at least 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: Evaluate risk vs benefit and consider alternative therapy after gastric bypass, sleeve gastrectomy, and gastric banding; weight gain may occur (Apovian 2015).

• Cardiac disease: Concurrent use with peroxisome proliferator-activated receptor (PPAR)-gamma agonists, including thiazolidinediones 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.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• 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 (NPO), 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. Premixed insulin formulations should generally be avoided in hospitalized patients due to frequent changes in nutritional status, and an increased risk of hypoglycemia when premixed insulin is given in patients who are NPO or not eating. 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 2019).

Dosage form specific issues:

• Multiple dose injection pens: According to the Centers for Disease Control and Prevention, 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).

Other warnings/precautions:

• Administration: Insulin NPH and insulin regular combination products are NOT intended for IV or IM administration or administration in an insulin infusion pump.
• Appropriate use: Not recommended for treatment of diabetic ketoacidosis (Kitabchi 2009).
• Patient education: Diabetes self-management education (DSME) is essential to maximize the effectiveness of therapy.

Monitoring Parameters

Diabetes mellitus: Plasma glucose (typically before meals and snacks and at bedtime; occasionally additional monitoring may be required), electrolytes, HbA_1c (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 2019]); 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).

Pregnancy

Pregnancy Considerations

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 HbA_1c 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). Also refer to individual monographs for additional information.

Patient Education

What is this drug used for?

• It is used to lower blood sugar in patients with high blood sugar (diabetes).

Frequently reported side effects of this drug

• Injection site irritation

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• 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.
• Anxiety
• Vision changes
• Chills
• Severe dizziness
• Passing out
• Mood changes
• Seizures
• Slurred speech
• Shortness of breath
• Excessive weight gain
• Swelling of arms or legs
• Injection site thick skin, pits, or lumps
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of 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 brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.