Insulin Glargine

Insulin glargine is a prescription medication used to treat type 1 and type 2 diabetes. Insulin glargine, a long-acting form of insulin, works by replacing the insulin that is normally produced by the body and by helping the body to use sugar for energy. It also stops the liver from producing more sugar.

This medication comes in an injectable form to be injected under the skin. Insulin glargine is usually injected once daily.

Common side effects include low blood sugar, redness and skin thickening at the injection site, and weight gain.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Insulin glargine falls into category C. In animal studies, pregnant animals were given insulin glargine, and some babies had problems.

Never share an injection pen or syringe with another person, even if the needle has been changed.

Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

The Toujeo brand of insulin glargine contains 3 times as much insulin per milliliter (mL) as the Lantus or Basaglar brands. There are 300 units of insulin in 1 mL of Toujeo, and 100 units in 1 mL of Lantus or Basaglar.

If there are any changes in the brand, strength, or type of insulin you use, your dosage needs may change.

Insulin is injected under the skin. You will be shown how to use injections at home. Do not give yourself this medicine if you do not understand how to use the injection and properly dispose of used needles and syringes.

Insulin glargine must not be given with an insulin pump, or mixed with other insulins. Do not inject insulin glargine into a vein or a muscle.

Insulin glargine is usually injected once per day at the same time each day. You will be shown how to use injections at home. Do not give yourself this medicine if you do not understand how to use the injection and properly dispose of used needles and syringes.

Your care provider will show you the best places on your body to inject insulin glargine. Use a different place each time you give an injection. Do not inject into the same place two times in a row.

If you use an injection pen, use only the injection pen that comes with insulin glargine. Attach a new needle before each use. Do not transfer the insulin from the pen into a syringe.

Never share an injection pen or syringe with another person, even if the needle has been changed. Sharing these devices can allow infections or disease to pass from one person to another.

Use a disposable needle and syringe only once. Follow any state or local laws about throwing away used needles and syringes. Use a puncture-proof "sharps" disposal container (ask your pharmacist where to get one and how to throw it away). Keep this container out of the reach of children and pets.

Low blood sugar (hypoglycemia) can happen to everyone who has diabetes. Symptoms include headache, hunger, sweating, irritability, dizziness, nausea, fast heart rate, and feeling anxious or shaky. To quickly treat low blood sugar, always keep a fast-acting source of sugar with you such as fruit juice, hard candy, crackers, raisins, or non-diet soda.

Your doctor can prescribe a glucagon emergency injection kit to use in case you have severe hypoglycemia and cannot eat or drink. Be sure your family and close friends know how to give you this injection in an emergency.

Also watch for signs of high blood sugar (hyperglycemia) such as increased thirst or urination, blurred vision, headache, and tiredness.

Blood sugar levels can be affected by stress, illness, surgery, exercise, alcohol use, or skipping meals. Ask your doctor before changing your insulin dose or schedule.

Insulin glargine is only part of a treatment program that may also include diet, exercise, weight control, blood sugar testing, and special medical care. Follow your doctor's instructions very closely.

Keep this medicine in its original container protected from heat and light. Do not draw insulin from a vial into a syringe until you are ready to give an injection. Do not freeze insulin or store it near the cooling element in a refrigerator. Throw away any insulin that has been frozen.

Storing unopened (not in use) Basaglar or Lantus:

• Refrigerate and use until expiration date; or

• Store at room temperature and use within 28 days.

Storing unopened (not in use) Toujeo:

• Refrigerate and use until expiration date.

Storing opened (in use) Basaglar or Lantus:

• Store the vial in a refrigerator or at room temperature and use within 28 days.

• Store the injection pen at room temperature (do not refrigerate) and use within 28 days.

Storing opened (in use) Toujeo:

• Store the injection pen at room temperature (do not refrigerate) and use within 42 days.

Do not store an injection pen with the needle attached.

Do not use the medicine if it looks cloudy, has changed colors, or has any particles in it. Call your pharmacist for new medicine.

Wear a diabetes medical alert tag in case of emergency. Any medical care provider who treats you should know that you have diabetes.

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]

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.

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 Insulin. Exceptions: Levobunolol; Metipranolol. Monitor therapy

DPP-IV Inhibitors: May enhance the hypoglycemic effect of Insulin. Management: Consider a decrease in insulin dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Consider therapy modification

Edetate CALCIUM Disodium: May enhance the hypoglycemic effect of Insulin. Monitor therapy

Edetate Disodium: May enhance the hypoglycemic effect of Insulin. Monitor therapy

GLP-1 Agonists: May enhance the hypoglycemic effect of Insulin. Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Avoid the use of lixisenatide in patients receiving both basal insulin and a sulfonylurea. 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 Insulin. 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

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

Metreleptin: May enhance the hypoglycemic effect of Insulin. 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

Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Pioglitazone: May enhance the adverse/toxic effect of Insulin. 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 Insulin. 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

Quinolone Antibiotics: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolone Antibiotics 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

Rosiglitazone: Insulin 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

SGLT2 Inhibitors: May enhance the hypoglycemic effect of Insulin. 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

Applies to insulin glargine: subcutaneous solution

General

Adverse reactions associated with insulin glargine include hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, pruritus, rash, edema, and weight gain.[Ref]

Metabolic

The ORIGIN (Outcome Reduction with Initial Glargine Intervention) trial, an open-labeled, randomized study comparing insulin glargine to standard care in persons 50 years or older with abnormal glucose levels (impaired fasting glucose and/or impaired glucose tolerance) or early type 2 diabetes mellitus and established cardiovascular (CV) disease or CV risk factors, found over the course of the 6 year study, severe hypoglycemia occurred in 5.7% of patients receiving insulin glargine compared to 1.9% in the standard care group. The median HbA1c values in the insulin glargine group ranged from 5.9% to 6.4% while the HbA1c values in the standard care group ranged from 6.2% to 6.6%. The incidence for all hypoglycemia was 58% and 26% in the insulin glargine and standard groups, respectively.

Weight gain has been reported with insulin therapy and has been attributed to the anabolic effects of insulin and the decrease in glucosuria. In the ORIGIN trial, the median change in body weight from baseline to the last treatment visit was 2.2 kg greater in the insulin glargine group (+1.4 kg vs -0.8 kg).[Ref]

Very common (10% or more): Hypoglycemia
Frequency not reported: Weight gain[Ref]

Local

Injection site reactions include redness, pain, itching, hives, swelling, or inflammation. In some cases, these reactions may be caused by other factors, such as irritants in skin cleansing agents. In clinical studies, there was a higher incidence of treatment-emergent injection site pain in insulin-glargine treated patients compared to NPH-treated patients (2.7% vs 0.7%).[Ref]

Common (1% to 10%): Injection site reactions, injection site pain[Ref]

Hypersensitivity

Hypersensitivity side effects have included both local and systemic reactions. Anaphylaxis has been reported. Local reactions have presented as erythema, local edema, and pruritus at the injection site. Most minor reactions to insulin at the injection site resolve in a few days to a few weeks.[Ref]

Rare (less than 0.1%): Allergic reactions[Ref]

Cardiovascular

Very common (10% or more): Hypertension (up to 19.6%)
Common (1% to 10%): Peripheral edema[Ref]

Insulin may cause sodium retention and edema, especially as metabolic control is improving. The ORIGIN (Outcome Reduction with Initial Glargine Intervention) trial, an open-labeled, randomized study in persons 50 years or older with abnormal glucose levels (impaired fasting glucose and/or impaired glucose tolerance) or early type 2 diabetes mellitus and established cardiovascular (CV) disease or CV risk factors, found the time to first occurrence of a major adverse cardiovascular event (MACE) and the incidence of MACE to be similar between insulin glargine and standard care (n=12.537).[Ref]

Dermatologic

Postmarketing reports indicate children and adolescents may experience more skin reactions such as rash and urticaria, than adults.[Ref]

Common (1% to 10%): Lipohypertrophy
Uncommon (0.1% to 1%): Lipoatrophy
Postmarketing reports: Rash urticaria[Ref]

Oncologic

Frequency not reported: Cancer occurrence[Ref]

The ORIGIN (Outcome Reduction with Initial Glargine Intervention) trial, an open-labeled, randomized study in persons 50 years or older with abnormal glucose levels (impaired fasting glucose and/or impaired glucose tolerance) or early type 2 diabetes mellitus and established cardiovascular (CV) disease or CV risk factors, comparing insulin glargine to standard care found the overall incidence of all types of cancer combined or death from cancers was similar between treatment groups (n=12,537). In July 2009, The US FDA reported on an ongoing safety review evaluating a possible increased risk of cancer. In February 2011, the FDA in an updated communication reported the evidence was inconclusive and it is not possible to conclude that the use of this insulin increases the risk of cancer.[Ref]

Immunologic

Frequency not reported: Antibody formation[Ref]

As with all therapeutic proteins, the potential for immunogenicity exits. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay and may be influenced by assay methodology, sample handling and collection, concomitant medications, and underlying disease. The presence of insulin antibodies may increase or decrease the efficacy of insulin and may require dose adjustment.[Ref]

Ocular

Rare (less than 0.1%): Visual impairment, retinopathy[Ref]

Rapid improvement in glucose control has been associated with a transitory, reversible ophthalmologic refraction disorder and worsening of diabetic retinopathy. However, long-term glycemic control decreases the risk.[Ref]

Gastrointestinal

Common (1% to 10%): Gastroenteritis[Ref]

Musculoskeletal

Rare (less than 0.1%): Myalgia[Ref]

Nervous system

Common (1% to 10%): Headache
Very rare (less than 0.01%): Dysgeusia
Frequency not reported: Peripheral neuropathy[Ref]

Rapid improvement in glucose control has been associated with a transitory, reversible acute painful peripheral neuropathy. However, long-term glycemic control decreases the risk.[Ref]

Respiratory

Very common (10% or more): Upper respiratory infection (up to 22.4%)
Common (1% to 10%): Pharyngitis, rhinitis, sinusitis[Ref]

Some side effects of insulin glargine may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Dose should be individualized based on clinical response; this basal insulin should be used in regimens with short-acting insulin
Initial dose: One-third to one-half the total daily insulin requirement subcutaneously once a day
Maintenance dose: Dose should be adjusted according to metabolic needs, blood glucose measurements, and glycemic goals
Maximum dose: 80 units per 1 injection; if a dose greater than 80 units is needed, it should be be given as 2 or more injections

U-300:
-Metabolic needs during the first 24 hours may not be fully covered with the first U-300 dose; monitor closely
-Dose titration should occur no more frequently than every 3 to 4 days due to the longer time for U-300 to achieve steady-state
Maximum dose: 80 units per 1 injection

Conversion of U-100 to U-300: Initial dose should be the same, however for patients controlled on U-100, expect a higher daily dose of U-300 to maintain the same level of glycemic control.

Conversion of NPH insulin to insulin glargine:
-From ONCE-DAILY NPH insulin: Initial insulin glargine dose should be the same dose of NPH that is being discontinued
-From TWICE-DAILY NPH insulin: Initial insulin glargine dose should be 80% of the total NPH dose that is being discontinued

Comments:
-The initial total daily insulin requirement in insulin naive patients is generally 0.2 to 0.4 units of insulin per kilogram of body weight.
-When changing treatment regimens, the dose and frequency of short-acting insulin may need to be adjusted.
-To minimize hypoglycemia, closely monitor blood glucose, especially with changing regimens.
-During clinical trials, patients treated with U-300 used 17.5% more basal insulin than patients treated with U-100.

Use: To improve glycemic control in patients with type 1 diabetes mellitus.

Initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemic reactions.

Use with caution; frequent glucose monitoring and insulin dose reduction may be required

Use with caution; frequent glucose monitoring and insulin dose reduction may be required

Data not available