Insulin Glargine

Special Alerts

Insulin Pen Safety Alert October 2017 The Institute for Safe Medication Practices (ISMP) National Medication Errors Reporting Program (MERP) has issued a safety alert regarding reports of patients incorrectly using insulin pens at home, resulting in severe cases of hyperglycemia. Patients were not removing the inner cover of a standard insulin pen needle prior to attempting to administer the insulin, and thus were not receiving insulin doses.

Health care professionals should instruct patients on the proper use of insulin pens and require patient demonstration to verify understanding. They should also verify which pen needles patients will be using at home, either standard pens or pens with automatic needle retraction devices, and tailor instruction accordingly.

More information can be found at http://www.ismp.org/NAN/files/NAN-20171012.pdf.

Brand Names: US

Basaglar KwikPen Lantus Lantus SoloStar Toujeo SoloStar

Pharmacologic Category

Insulin, Long-Acting

Dosing: Adult

Note: Insulin glargine is a long-acting insulin administered by SubQ injection. Insulin glargine is approximately equipotent to human insulin, but has a slower onset, no pronounced peak, and a longer duration of activity. Insulin requirements vary dramatically between patients and dictates frequent monitoring and close medical supervision. Diabetes mellitus, type 1: SubQ:

Insulin glargine-specific dosing: Initial dose: Approximately one-third to one-half of the total daily insulin requirement administered once daily. A rapid-acting or short-acting insulin should also be used to complete the balance (~1/2 to 2/3) of the total daily insulin requirement. Adjust dosage according to patient response.

Conversion to insulin glargine from other insulin therapies:

Converting from once-daily NPH insulin to insulin glargine: May be substituted on an equivalent unit-per-unit basis

Converting from twice-daily NPH insulin to insulin glargine: Initial dose: Use 80% of the total daily dose of NPH (eg, 20% reduction); administer once daily; adjust dosage according to patient response

Conversion between Toujeo, Lantus, and Basaglar:

Conversion from once-daily Toujeo to once-daily Lantus or once-daily Basaglar: Initial dose: Use 80% of the dose of Toujeo (eg, 20% reduction); adjust dosage according to patient blood glucose response.

Conversion from once-daily Lantus to once-daily Toujeo or once-daily Basaglar: Initial dose: May be substituted on an equivalent unit-per- unit basis; however, generally a higher daily dosage of Toujeo will be required to achieve the same level of glycemic control as with Lantus.

General insulin dosing (off-label):

Type 1: SubQ: Note: Multiple daily doses are utilized and guided by blood glucose monitoring. Combinations of insulin formulations are commonly used. The daily doses presented below are expressed as the total units/kg/day of all insulin formulations used. Insulin glargine must be used in combination with a rapid- or short-acting insulin.

Initial total insulin dose: 0.2 to 0.6 units/kg/day in divided doses. Conservative initial doses of 0.2 to 0.4 units/kg/day are often recommended to avoid the potential for hypoglycemia.

Usual maintenance range: 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

Division of daily insulin requirement ("conventional therapy"): Generally, 50% to 75% of the total daily dose (TDD) is given as an intermediate-acting or a long-acting form of insulin (eg, insulin glargine) (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 (eg, lispro, aspart, glulisine) or short-acting (regular) form of insulin.

Division of daily insulin requirement ("intensive therapy"): Basal insulin delivery with 1 or 2 doses of intermediate-acting or long- acting insulin formulations superimposed with doses of short-acting (regular) insulin or rapid-acting insulin (eg, lispro, aspart, glulisine) formulations 3 or more times daily.

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.

Diabetes mellitus, type 2: SubQ:

Insulin glargine-specific dosing:

Manufacturer’s labeling: Initial basal insulin dose: 0.2 units/kg once daily; for Lantus or Basaglar, up to 10 units/day initially is recommended. Adjust dosage according to patient response

Conversion to insulin glargine from other insulin therapies:

Converting from once-daily NPH insulin to insulin glargine: May be substituted on an equivalent unit-per-unit basis Converting from twice-daily NPH insulin to insulin glargine: Initial dose: Use 80% of the total daily dose of NPH (eg, 20% reduction); administer once daily; adjust dosage according to patient response

Conversion between Toujeo, Lantus, or Basaglar:

Alternate recommendations (off-label):

Initial: 10 units or 0.1 to 0.2 units/kg once daily, usually in combination with metformin +/- other noninsulin agent (ADA 2017f). Alternatively, if HbA1c >8% prior to initiation of basal insulin, 0.2 to 0.3 units/kg once daily is recommended (Garber [AACE/ACE 2016]).

Dosage adjustment:

To reach fasting blood glucose target: Adjust dose by 10% to 15% or 2 to 4 units; may adjust at weekly or twice weekly intervals (ADA 2017f)

For hypoglycemia: If no clear reason for hypoglycemia, decrease dose by 4 units or by 10% to 20% (ADA 2017f)

Surgical patients: On the morning of surgery or procedure, give 60% to 80% of the usual dose of long-acting analogs (eg, detemir, glargine, or degludec) (ADA 2017d)

General considerations for insulin use in type 2 diabetes (off-label):

Timing of initiation: Dual therapy (metformin + a second antihyperglycemic agent) and then triple therapy (metformin + two antihyperglycemic agents) is recommended in patients who fail to achieve glycemic goals after ~3 months with lifestyle intervention and metformin monotherapy or dual therapy, respectively (unless contraindications to metformin exist). Preference is not given for which agent(s) should be added to metformin (drug choice should be individualized based on patient characteristics). If HbA1c target not achieved after ~3 months of triple therapy, consider initiating basal insulin (usually with metformin +/- other noninsulin agent) or if patient already receiving an optimally titrated basal insulin (ie, a long-acting insulin such as glargine, degludec, or detemir) as part of their regimen, consider combination injectable therapy (ADA 2017f).

Combination injectable therapy: If HbA1c target has not been met with basal insulin (ie, long-acting insulin such as glargine, degludec or detemir) (usually combined with metformin +/- other noninsulin agent), despite titrating basal insulin to provide acceptable fasting blood glucose concentrations, combination injectable therapy should be considered. Options include: adding a rapid-acting insulin (eg, lispro, aspart, glulisine) prior to largest meal or adding a GLP-1 receptor agonist or changing from basal insulin to a twice daily premixed insulin. If HbA1c still not adequately controlled, consider advancing from one rapid-acting insulin prior to largest meal to ‘basal-bolus’ regimen (ie, rapid-acting insulin administered before ≥2 meals) or consider advancing from a twice daily premixed insulin to a 3 times daily premixed insulin (ADA 2017f).

Patients with elevated HbA1C at therapy initiation: If HbA1c is ≥9% at initiation of therapy, dual therapy (metformin + a second antihyperglycemic agent) should be considered. If HbA1c ≥10%, blood glucose is ≥300 mg/dL or if patient is symptomatic (eg, polyuria, polydipsia), insulin therapy (with or without additional agents) should be considered (ADA 2017f).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Insulin glargine is a long-acting insulin administered by SubQ injection. Insulin glargine is approximately equipotent to human insulin, but has a slower onset, no pronounced peak, and a longer duration of activity. Changing the basal insulin component from another insulin to insulin glargine can be done on a unit-to-unit basis. Insulin requirements vary dramatically between patients and dictates frequent monitoring and close medical supervision. See Insulin Regular for additional information.

Insulin glargine-specific dosing:

Type 1 diabetes mellitus: Children ≥6 years and Adolescents: SubQ: Initial dose: Approximately one-third of the total daily insulin requirement; a rapid-acting or short-acting insulin should also be used.

Type 1 or type 2 diabetes; previously receiving basal insulin plus bolus insulin (eg, NPH + regular insulin):

Children <6 years: SubQ: Limited data available: 40% of the established total daily insulin requirement; this resulted in a reduction in hypoglycemic episodes in 35 nonobese preschool-aged children (age range: 2.6-6.3 years) when used in conjunction with a rapid-acting insulin prior to meals (Alemzadeh, 2005).

Children ≥6 years: SubQ:

Converting from once-daily NPH insulin: May be substituted on an equivalent unit-per-unit basis

Converting from twice-daily NPH insulin: Initial dose: Use 80% of the total daily dose of NPH (eg, 20% reduction); administer once daily; adjust dosage according to patient response

General insulin dosing (off-label):

Type 1 diabetes mellitus: Children and Adolescents: Note: Multiple daily doses are utilized and guided by blood glucose monitoring. Combinations of insulin formulations are commonly used. The daily doses presented below are expressed as the total units/kg/day of all insulin formulations used. Insulin glargine must be used in combination with a short-acting insulin.

Usual maintenance range: SubQ: 0.5-1 unit/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)

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer’s labeling; insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling; insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.

Dosing: Obesity

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

Use: Labeled Indications

Diabetes mellitus, types 1 and 2: To improve glycemic control in adults with type 1 diabetes mellitus (insulin dependent, IDDM) and type 2 diabetes mellitus (noninsulin, NIDDM); to improve glycemic control in children ≥6 years with type 1 diabetes mellitus (Lantus and Basaglar only)

Limitations of use: Not recommended for the treatment of diabetic ketoacidosis. Clinical Practice Guidelines

Diabetes Mellitus:

American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE), “Consensus Statement on the Comprehensive Type 2 Diabetes Management Algorithm- 2016 Executive Summary”, January 2016

American Diabetes Association, “Standards of Medical Care in Diabetes - 2017,” January 2017

Canadian Diabetes Association, “Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada,” 2013

Contraindications

Hypersensitivity to insulin glargine or any component of the formulation; during episodes of hypoglycemia

Documentation of allergenic cross-reactivity for insulin is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Warnings/Precautions: Comprehensive

Concerns related to adverse effects:

• Hypersensitivity: Severe, life-threatening allergic reactions, including anaphylaxis, may occur. If hypersensitivity reactions occur, discontinue therapy.

• Hypoglycemia: The most common adverse effect of insulin is hypoglycemia. The timing of hypoglycemia differs among various insulin formulations. Hypoglycemia may result from increased work or exercise without eating; use of long-acting insulin preparations (eg, insulin detemir, insulin glargine, insulin degludec) may delay recovery from 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. • 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:

• 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, 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.

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).

Other warnings/precautions:

• Administration: Insulin glargine is a clear solution, but it is NOT intended for IV or IM administration or via an insulin pump.

• Appropriate use: Diabetes mellitus: The general objective of exogenous insulin therapy is to approximate the physiologic pattern of insulin secretion which is characterized by two distinct phases. Phase 1 insulin secretion suppresses hepatic glucose production and phase 2 insulin secretion occurs in response to carbohydrate ingestion; therefore, exogenous insulin therapy may consist of basal insulin (eg, intermediate- or long-acting insulin), insulin administered via continuous subcutaneous insulin infusion [CSII]) and/or preprandial insulin (eg, short- or rapid-acting insulin) (see Related Information: Insulin Products). Patients with type 1 diabetes do not produce endogenous insulin; therefore, these patients require both basal and preprandial insulin administration. Patients with type 2 diabetes retain some beta-cell function in the early stages of their disease; however, as the disease progresses, phase 1 insulin secretion may become completely impaired and phase 2 insulin secretion becomes delayed and/or inadequate in response to meals. Therefore, patients with type 2 diabetes may be treated with oral antidiabetic agents, basal insulin, and/or preprandial insulin depending on the stage of disease and current glycemic control. Since treatment regimens often consist of multiple agents, dosage adjustments must address the specific phase of insulin release that is primarily contributing to the patient’s impaired glycemic control. Treatment and monitoring regimens must be individualized.

• Patient education: Diabetes self-management education (DSME) is essential to maximize the effectiveness of therapy.

Medication Safety Issues

Sound-alike/look-alike issues: Insulin glargine may be confused with insulin glulisine

Lantus may be confused with latanoprost, Latuda, Xalatan

High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error. Due to the number of insulin preparations, it is essential to identify/clarify the type of insulin to be used.

Administration issues: Insulin glargine is a clear solution, but it is NOT intended for IV or IM administration.

Other safety concerns: Cross-contamination may occur if insulin pens are shared among multiple patients. Steps should be taken to prohibit sharing of insulin pens.

International issues: Lantus [US, Canada, and multiple international markets] may be confused with Lanvis brand name for thioguanine [Canada and multiple international markets]

Administration: Subcutaneous

Do not use if solution is viscous or cloudy; use only if clear and colorless with no visible particles. Insulin glargine should be administered once daily, at any time of day; however, administer at the same time each day. Cold injections should be avoided. SubQ administration is usually made into the thighs, arms, buttocks, or abdomen; rotate injection sites within the same region to avoid lipodystrophy. Do not dilute or mix insulin glargine with any other insulin formulation or solution. Insulin glargine prefilled pens are available in concentrations of 100 units/mL and 300 units/mL. Prefilled pens are calibrated to display the actual insulin units administered (no dosage conversion needed) and will administer up to 80 units per injection. Do not use a syringe to withdraw concentrated insulin glargine (300 units/mL) from a prefilled pen for administration. Cartridges [Canadian product] are to be used only with re-usable pens recommended by the manufacturer (refer to product labeling).

Medication Patient Education with HCAHPS Considerations

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience injection site irritation. Have patient report immediately to prescriber signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating), signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat), vision changes, chills, severe dizziness, passing out, seizures, shortness of breath, excessive weight gain, swelling of arms or legs, or change in skin to thick or thin at injection site (HCAHPS).

• Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Dosage Forms

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

Solution, Subcutaneous:

Lantus: 100 units/mL (10 mL) [contains metacresol]

Solution Pen-injector, Subcutaneous:

Basaglar KwikPen: 100 units/mL (3 mL) [contains metacresol]

Lantus SoloStar: 100 units/mL (3 mL) [contains metacresol]

Toujeo SoloStar: 300 units/mL (1.5 mL) [contains metacresol]

Dosage Forms: Canada Information with regard to form, strength, and availability of products uniquely available in Canada but currently not available in the US. Refer also to Dosage Forms.

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

Solution, Injection:

Basaglar: 100 units/mL (cartridge) (3 mL) [contains metacresol]

Monitoring Parameters

Diabetes mellitus: Plasma glucose, 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 2017a]), potassium (in patients at risk for hypokalemia); renal function; hepatic function; weight

Advanced Practitioners Physical Assessment/Monitoring

Obtain HbA1c (at least twice annually if meeting goals and quarterly for patients not meeting treatment goals or with therapy change), serum glucose, electrolytes, potassium, renal function tests, and liver function tests. Monitor weight. Monitor for hypoglycemia at regular intervals during therapy. Teach patient proper use, including appropriate injection technique and syringe/needle disposal, and monitoring requirements. Refer to dietician and/or diabetes self-management education.

Nursing Physical Assessment/Monitoring

Check ordered labs and report abnormalities. Monitor for hypoglycemia at regular intervals during therapy. Teach patient proper use, including appropriate injection technique and syringe/needle disposal, and monitoring requirements. Educate and instruct patient to report signs of hypoglycemia (dizziness, headache, fatigue, weakness, shaking, fast heartbeat, confusion, hunger, or sweating) or hypokalemia (muscle pain or weakness, muscle cramps, or an abnormal heartbeat). May need referral to dietician and/or diabetes self-management education.

Reference Range Recommendations for glycemic control in nonpregnant adults with diabetes (ADA 2017a):

HbA1c: <7% (a more aggressive [<6.5%] or less aggressive [<8%] HbA1c goal may be targeted based on patient-specific characteristics)

Preprandial capillary blood glucose: 80 to 130 mg/dL

Peak postprandial capillary blood glucose: <180 mg/dL

Recommendations for glycemic control in older adults (≥65 years) with diabetes (ADA 2017b):

HbA1c: <7.5% (healthy); <8% (complex/intermediate health); <8.5% (very complex/poor health) (individualization may be appropriate based on patient and caregiver preferences)

Preprandial capillary blood glucose: 90 to 130 mg/dL (healthy); 90 to 150 mg/dL (complex/intermediate health); 100 to 180 mg/dL (very complex/poor health)

Bedtime capillary blood glucose: 90 to 150 mg/dL (healthy); 100 to 180 mg/dL (complex/intermediate health); 110 to 200 mg/dL (very complex/poor health)

Recommendations for glycemic control in pediatric (all age groups) patients with type 1 diabetes (ADA 2017e):

HbA1c: <7.5% (individualization may be appropriate based on patient-specific characteristics; <7% is reasonable if it can be achieved without excessive hypoglycemia)

Preprandial capillary blood glucose: 90 to 130 mg/dL

Bedtime and overnight capillary blood glucose: 90 to 150 mg/dL

Recommendations for hospitalized adult patients with diabetes (ADA 2017d): Target glucose range: 140 to 180 mg/dL (majority of critically ill and noncritically ill patients; <140 mg/dL may be appropriate for selected patients, if it can be achieved without excessive hypoglycemia). Initiate insulin therapy for persistent hyperglycemia at ≥180 mg/dL

Recommendations for perioperative care in adult patients with diabetes (ADA 2017d): Target glucose range during perioperative period: Consider targeting 80 to 180 mg/dL

Drug Interactions: Metabolism/Transport Effects

None known.

Drug Interactions: Avoid Concomitant Use

Avoid concomitant use of Insulin Glargine with any of the following: Macimorelin; Rosiglitazone

Drug Interactions: Increased Effect/Toxicity

Insulin Glargine may increase the levels/effects of: Hypoglycemia-Associated Agents; Rosiglitazone

The levels/effects of Insulin Glargine may be increased by: Alpha-Lipoic Acid; Androgens; Antidiabetic Agents; Beta-Blockers; Dipeptidyl Peptidase-IV Inhibitors; Edetate CALCIUM Disodium; Edetate Disodium; Glucagon-Like Peptide-1 Agonists; Guanethidine; Herbs (Hypoglycemic Properties); Liraglutide; Metreleptin; Monoamine Oxidase Inhibitors; Pegvisomant; Pioglitazone; Pramlintide; Prothionamide; Quinolones; Salicylates; Selective Serotonin Reuptake Inhibitors; Sodium-Glucose Cotransporter 2 (SLGT2) Inhibitors

Drug Interactions: Decreased Effect

Insulin Glargine may decrease the levels/effects of: Macimorelin

The levels/effects of Insulin Glargine may be decreased by: Hyperglycemia-Associated Agents; Quinolones; Ritodrine; Thiazide and Thiazide-Like Diuretics

Storage/Stability

Basaglar:

Prefilled pens: Store unopened prefilled pens at room temperature <30°C (86°F) for 28 days, or refrigerated at 2°C to 8°C (36°F to 46°F) until expiration date. Once in use, store prefilled pens at room temperature <30°C (86°F) and use within 28 days; do not refrigerate. Do not freeze or use if previously frozen; protect from heat and light.

Cartridges [Canadian product]: Store unopened cartridges refrigerated at 2°C to 8°C (36°F to 46°F) until expiration date. Once in use, store cartridges at room temperature <30°C (86°F) and use within 28 days; do not refrigerate. Do not freeze or use if previously frozen; protect from heat and light.

Lantus: Store unopened vials and prefilled pens refrigerated at 2°C to 8°C (36°F to 46°F) until expiration date, or at room temperature <30°C (<86°F) for 28 days; do not freeze; protect from heat and sunlight. Once punctured (in use), store vials refrigerated or at room temperature <30°C (<86°F) and use within 28 days. Store prefilled pens (SoloStar) that have been punctured (in use) at temperatures <30°C (<86°F) and use within 28 days; do not freeze or refrigerate.

Toujeo: Store unopened prefilled pen (SoloStar) at 2°C to 8°C (36°F to 46°F) until expiration date; do not freeze. Store prefilled pens (SoloStar) that have been opened (in use) at <30°C (<86°F) and use within 42 days; do not freeze or refrigerate.

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. Insulin glargine differs from human insulin by adding two arginines to the C- terminus of the B-chain in addition to containing glycine at position A21 in comparison to the asparagine found in human insulin. Insulins are categorized based on the onset, peak, and duration of effect (eg, rapid-, short-, intermediate-, and long-acting insulin). Insulin glargine is a long-acting insulin analog.

Pharmacodynamics/Kinetics

Note: Onset and duration of hypoglycemic effects depend upon the route of administration (adsorption and onset of action are more rapid after deeper IM injections than after SubQ), site of injection (onset and duration are progressively slower with SubQ injection into the abdomen, arm, buttock, or thigh respectively), volume and concentration of injection, and the preparation administered. Rate of absorption, onset, and duration of activity may be affected by exercise, presence of lipodystrophy, local blood supply, and/or temperature.

Onset of action: Lantus: 3 to 4 hours; Toujeo: 6 hours

Peak effect: Lantus, Basaglar: No pronounced peak

Duration: Lantus, Basaglar: Generally 24 hours or longer; reported range (Lantus): 10.8 to >24 hours (up to ~30 hours documented in some studies) (Heinemann 2000)

Absorption: Slow; upon injection into the subcutaneous tissue, microprecipitates form which allow small amounts of insulin glargine to release over time

Metabolism: Partially metabolized in the subcutaneous depot at the carboxyl terminus of the B chain to form two active metabolites, M1 (21A-Gly-insulin) and M2 (21A- Gly-des-30B-Thr-insulin)

Time to peak, plasma: Lantus: No pronounced peak; Basaglar: ~12 hours

Excretion: Urine

Adverse Reactions

Primarily symptoms of hypoglycemia.

>10%

Cardiovascular: Hypertension (20%), peripheral edema (20%)

Central nervous system: Depression (11%)

Endocrine & metabolic: Hypoglycemia (Type I on combination regimens: ≤69%; Type II on combination regimens: ≤8%; monotherapy in adults ≥50 years old: 6% [ORIGIN trial])

Gastrointestinal: Diarrhea (11%)

Genitourinary: Urinary tract infection (11%)

Immunologic: Antibody development (20% to 44%; effect on therapy not reported)

Infection: Influenza (19%), infection (9% to 14%)

Neuromuscular & skeletal: Arthralgia (14%), back pain (13%), limb pain (13%)

Ophthalmic: Cataract (18%), retinopathy (14%)

Respiratory: Upper respiratory tract infection (adults: 6% to 29%; children & adolescents: 14%), sinusitis (19%), bronchitis (15%), nasopharyngitis (7% to 13%), cough (12%)

1% to 10%:

Cardiovascular: Retinal vascular disease (6%)

Central nervous system: Headache (6% to 10%)

Local: Pain at injection site (3%)

Respiratory: Pharyngitis (children & adolescents: 8%), rhinitis (children & adolescents: 5%)

Miscellaneous: Accidental injury (6%)

Frequency not defined:

Endocrine & metabolic: Sodium retention

Local: Erythema at injection site, itching at injection site, localized edema, swelling at injection site

<1%, postmarketing, and/or case reports: Anaphylaxis, angioedema, bronchospasm, hyperglycemia, hypersensitivity reaction, hypertrophy at injection site, hypokalemia, hypotension, injection site reaction (including urticaria and inflammation), lipoatrophy at injection site, lipoatrophy at injection site, shock, skin rash, weight gain Dietary Considerations

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

Related Information

Diabetes Mellitus and Pregnancy Insulin Products Perioperative Management of the Diabetic Patient

Pregnancy Considerations

In women with diabetes, maternal hyperglycemia can be associated with congenital malformations as well as adverse effects in the fetus, neonate, and the mother (ACOG 2005; ADA 2018c; Metzger 2007). 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 2018c; Blumer 2013; Lambert 2013).

Insulin requirements tend to fall during the first trimester of pregnancy and increase in the later trimesters, peaking at 28 to 32 weeks' gestation. Following delivery, insulin requirements decrease rapidly (ACOG 2005).

Insulin therapy is the preferred treatment of type 1 and type 2 diabetes in pregnant women, as well as GDM when pharmacologic therapy is needed (ACOG 190 2018; ADA 2018c). Because insulin glargine has an increased affinity to the insulin-like growth factor (IGF-I) receptor, there are theoretical concerns that it may contribute to adverse events when used during pregnancy (Jovanovic 2007; Lambert 2013), although this has not been observed in available studies (Lambert 2013; Lepercq 2012; Pollex 2011). Women who are stable on insulin glargine prior to conception may continue it during pregnancy. Theoretical concerns of insulin glargine should be discussed prior to conception (Blumer 2013).

Breast-Feeding Considerations

In a study using insulin glargine, both exogenous and endogenous insulin were present in breast milk (Whitmore 2012). Breastfeeding is encouraged for all women, including those with type 1, type 2, or GDM (ACOG 2005; ADA 2018c; Blumer 2013; Metzger 2007). A small snack (such as milk) before breastfeeding may help decrease the risk of hypoglycemia in women with pregestational diabetes (ACOG 2005; Reader 2004). The manufacturer considers the use of insulin glargine to be compatible with breastfeeding, although adjustments of the mothers insulin dose may be needed.

Pregnancy & Lactation, In-Depth

Insulin Glargine

Allergy and Idiosyncratic Reactions

Insulin Preparations Allergy

Geriatric Considerations

Intensive glucose control (HbA1c <6.5%) has been linked to increased all-cause and cardiovascular mortality, hypoglycemia requiring assistance, and weight gain in adult type 2 diabetes. How "tightly" to control a geriatric patient's blood glucose needs to be individualized. Such a decision should be based on several factors, including the patient's functional and cognitive status, how well he/she recognizes hypoglycemic or hyperglycemic symptoms, and how to respond to them and other disease states. An HbA1c <7.5% is an acceptable endpoint for a healthy older adult, while <8% is acceptable for frail elderly patients, those with a duration of illness >10 years, or those with comorbid conditions and requiring combination diabetes medications. In patients with advanced microvascular complications and/or a life expectancy <5 years, a target HbA1c of 8% to 9% is reasonable. Patients who are unable to accurately draw up their dose will need assistance, such as prefilled syringes. Initial doses may require considerations for renal function in the elderly with dosing adjusted subsequently based on blood glucose monitoring. For elderly patients with diabetes who are relatively healthy, attaining target goals for aspirin use, blood pressure, lipids, smoking cessation, and diet and exercise may be more important than normalized glycemic control.

Dental: Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Dental: Effects on Dental Treatment Key adverse event(s) related to dental treatment: In general, morning appointments are advisable in patients with diabetes since endogenous cortisol levels are typically higher at this time; because cortisol increases blood sugar levels, the risk of hypoglycemia is less. It is important to confirm that the patient has eaten normally prior to the appointment and has taken all scheduled medications. If a procedure is planned with the expectation that the patient will alter normal eating habits ahead of time (eg, conscious sedation), diabetes medication dose may need to be modified in consultation with the patient’s physician. Patients with well-controlled diabetes can usually be managed conventionally for most surgical procedures. Although patients with diabetes usually recognize signs and symptoms of hypoglycemia and self-intervene before changes in or loss of consciousness occurs, they may not. Staff should be trained to recognize the signs (eg, unusual behavior or profuse sweating in patients who have diabetes) and treat patients who have hypoglycemia; a glucometer should be used to test patient blood glucose levels. Every dental office should have a protocol for managing hypoglycemia in conscious and unconscious patients. Having snack foods or oral glucose tablets or gels available, especially in practices where a large number of surgical procedures are performed, is also prudent (American Diabetes Association 2017).

Dental: Effects on Bleeding

No information available to require special precautions

Pronunciation

(IN soo lin GLAR jeen)

Brand Names: Canada

Basaglar Lantus Toujeo SoloStar

Brand Names: International

Abasaglar (DK, EE, ES, GB, HR, LT, NL, NO, PL, PT, SK) Abasria (MT) Basagine (PH) Basaglar (ID, SG) Basaglar KwikPen (PH) Basalin (TH) Basalog (MY) Bonglixan (CR, DO, GT, HN, MX, NI, PA, SV) Glargilin (PH) Glaritus (PH, VN) Insulet GN (BD) Lantus (AE, AR, AT, AU, BB, BE, BG, BH, BM, BR, BS, BZ, CH, CL, CN, CO, CR, CY, CZ, DE, DK, DO, EC, EE, ES, FI, FR, GB, GR, GT, GY, HK, HN, HR, HU, ID, IE, IL, IN, IS, IT, JM, JO, KR, KW, LB, LK, LT, LU, LV, MT, MX, MY, NI, NL, NO, NZ, PA, PE, PH, PK, PL, PR, PT, PY, QA, RO, RU, SA, SE, SG, SI, SK, SR, SV, TH, TR, TT, TW, UA, UY, VE, VN, ZW) Lantus XR (JP) Optisulin (CZ, EE, FI, IE, IN, LT, MT, NL, PL, PT, RO) Toujeo (SG) Tozheo (UA) Tuojeo (GB, HK, HR, IE, MY, NL, PH, SK) Vibrenta (BD)

Generic Available (US)

Pricing

Solution (Lantus Subcutaneous)

100 units/mL (10 mL): $307.16

Solution Pen-injector (Basaglar KwikPen Subcutaneous)

100 units/mL (3 mL): $78.32

Solution Pen-injector (Lantus SoloStar Subcutaneous)

100 units/mL (3 mL): $92.15

Solution Pen-injector (Toujeo SoloStar Subcutaneous)

300 units/mL (1.5 mL): $141.44 Disclaimer: The pricing data provide a representative AWP and/or AAWP price from a single manufacturer of the brand and/or generic product, respectively. The pricing data should be used for benchmarking purposes only, and as such should not be used to set or adjudicate any prices for reimbursement or purchasing functions. Pricing data is updated monthly.

FDA Approval Date

2000-04-20 References

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Index Terms

Glargine Insulin