Side Effects of Lantus (insulin glargine)

Lantus (insulin glargine) is a bioengineered (man-made) injectable form of long-acting insulin used to regulate sugar (glucose) levels in type 1 and type 2 diabetes. 

Individuals with type 1 diabetes do not produce insulin on their own; and individuals with type 2 diabetes do not produce enough insulin, or insulin is not as effective due to insulin resistance. 

Lantus works the same way as natural human insulin, but its action lasts longer. It helps diabetic patients regulate glucose or sugar in the body. Lantus works by promoting movement of sugar from blood into body tissues and also stops sugar production in liver.

Common side effects of Lantus include

• decreased blood sugar,
• injection site reactions (pain, rash, itching, redness, irritation),
• water retention in the joints, and
• weight gain.

Long-term use of Lantus can lead to thickening of fat tissues at the injection site.

Serious side effects of Lantus include severe

• allergic reactions (swelling under the skin, very low blood pressure, and bronchospasm).

Drug interactions of Lantus include the following because these drugs can increase the blood-sugar-lowering effect of Lantus:

• pramlintide,
• disopyramide,
• fenofibrate,
• fluoxetine, and
• aspirin. 

Other drugs that can decrease the blood-sugar-lowering effect of Lantus are

• corticosteroids like prednisone and hydrocortisone,
• niacin,
• isoniazid,
• diuretics like hydrochlorothiazide and furosemide,
• estrogens and progesterone in oral contraceptives, and
• albuterol. 

Safe and effective use of Lantus is not established for pregnant females. 

It is unknown if Lantus enters breast milk; therefore, it should be used with caution in females who are breastfeeding.

Common side effects of insulin glargine are:

• Decreased blood sugar and injection site pain
• Water retention in the joints and weight gain

Local allergic reactions that may occur at the injection sites are:

• Rash
• Itching
• Redness
• Irritation

Long term use of insulin glargine can lead to thickening of fat tissues at the injection site.

Severe allergic reactions are:

• Swelling under the skin
• Very low blood pressure
• Bronchospasm (tightening of chest that leads to difficulty breathing)

Individuals should contact a healthcare professional if they experience any of the above reactions.

The following adverse reactions are discussed elsewhere:

• Hypoglycemia
• Hypersensitivity and allergic reactions
• Hypokalemia

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trial of another drug and may not reflect the rates observed in practice.

The data in Table 1 reflect the exposure of 2327 patients with type 1 diabetes to Lantus or NPH. The type 1 diabetes population had the following characteristics:

• Mean age was 38.5 years.
• Fifty four percent were male, 96.9% were Caucasian, 1.8 % were Black or African American and 2.7 % were Hispanic.
• The mean BMI was 25.1 kg/m².

The data in Table 2 reflect the exposure of 1563 patients with type 2 diabetes to Lantus or NPH. The type 2 diabetes population had the following characteristics:

• Mean age was 59.3 years.
• Fifty eight percent were male, 86.7% were Caucasian, 7.8 % were Black or African American and 9 % were Hispanic.
• The mean BMI was 29.2 kg/m².

The frequencies of adverse events during Lantus clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in the tables below.

Table 1: Adverse Events in Pooled Clinical Trials up to 28 Weeks Duration in Adults with Type 1 Diabetes (adverse events with frequency ≥5%)

Table 2: Adverse Events in Pooled Clinical Trials up to 1 Year Duration in Adults with Type 2 Diabetes (adverse events with frequency ≥5%)

Table 3: Adverse Events in a 5-year Trial of Adults with Type 2 Diabetes (adverse events with frequency ≥10%)

Table 4: Adverse Events in a 28-Week Clinical Trial of Children and Adolescents with Type 1 Diabetes (adverse events with frequency ≥5% )

Severe Hypoglycemia

• Hypoglycemia is the most commonly observed adverse reaction in patients using insulin, including Lantus.
• Tables 5, and 6 and 7 summarize the incidence of severe hypoglycemia in the Lantus individual clinical trials. Severe symptomatic hypoglycemia was defined as an event with symptoms consistent with hypoglycemia requiring the assistance of another person and associated with either a blood glucose below 50 mg/dL (≤56 mg/dL in the 5-year trial and ≤36 mg/dL in the ORIGIN trial) or prompt recovery after oral carbohydrate, intravenous glucose or glucagon administration.
• Percentages of Lantus-treated adult patients experiencing severe symptomatic hypoglycemia in the Lantus clinical trials were comparable to percentages of NPH-treated patients for all treatment regimens (see Tables 5 and 6).
• In the pediatric phase 3 clinical trial, children and adolescents with type 1 diabetes had a higher incidence of severe symptomatic hypoglycemia in the two treatment groups compared to the adult trials with type 1 diabetes.

Table 5: Severe Symptomatic Hypoglycemia in Patients with Type 1 Diabetes

Table 6: Severe Symptomatic Hypoglycemia in Patients with Type 2 Diabetes

Table 7 displays the proportion of patients experiencing severe symptomatic hypoglycemia in the Lantus and Standard Care groups in the ORIGIN Trial.

Table 7: Severe Symptomatic Hypoglycemia in the ORIGIN trial

Peripheral Edema

• Some patients taking Lantus have experienced sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy.

Lipodystrophy

• Administration of insulin subcutaneously, including Lantus, has resulted in lipoatrophy (depression in the skin) or lipohypertrophy (enlargement or thickening of tissue) in some patients.

Insulin Initiation And Intensification Of Glucose Control

• Intensification or rapid improvement in glucose control has been associated with a transitory, reversible ophthalmologic refraction disorder, worsening of diabetic retinopathy, and acute painful peripheral neuropathy.
• However, long-term glycemic control decreases the risk of diabetic retinopathy and neuropathy.

Weight Gain

• Weight gain has occurred with some insulin therapies including Lantus and has been attributed to the anabolic effects of insulin and the decrease in glucosuria.

Allergic Reactions

Local allergy

• As with any insulin therapy, patients taking Lantus may experience injection site reactions, including
  • redness,
  • pain,
  • itching,
  • urticaria,
  • edema, and
  • inflammation.
• In clinical studies in adult patients, there was a higher incidence of treatment-emergent injection site pain in Lantus-treated patients (2.7%) compared to NPH insulin-treated patients (0.7%).
• The reports of pain at the injection site did not result in discontinuation of therapy.

Systemic allergy

• Severe, life-threatening, generalized allergy, including
  • anaphylaxis,
  • generalized skin reactions,
  • angioedema,
  • bronchospasm,
  • hypotension, and
  • shock may occur with any insulin, including Lantus and may be life threatening.

Immunogenicity

• As with all therapeutic proteins, there is potential for immunogenicity.
• All insulin products can elicit the formation of insulin antibodies.
• The presence of such insulin antibodies may increase or decrease the efficacy of insulin and may require adjustment of the insulin dose.
• In phase 3 clinical trials of Lantus, increases in titers of antibodies to insulin were observed in NPH insulin and Lantus treatment groups with similar incidences.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of Lantus.

• Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
• Medication errors have been reported in which other insulins, particularly rapid-acting insulins, have been accidentally administered instead of Lantus.
• To avoid medication errors between Lantus and other insulins, patients should be instructed to always verify the insulin label before each injection.

Table 8 includes clinically significant drug interactions with Lantus.

Table 8: Clinically Significant Drug Interactions with Lantus