Side Effects of Tresiba (Insulin Degludec Injection), Warnings, Uses (2023)

What Is Tresiba

Tresiba (insulin degludec injection) is a long-acting human insulin analog indicated to improve glycemic control in adults with diabetes mellitus.

What Are Side Effects of Tresiba?

Common side effects of Tresiba include:

• low blood sugar (hypoglycemia),
• allergic reactions,
• injection site reactions,
• body fat redistribution (lipodystrophy),
• itching,
• rash,
• swelling,
• weight gain,
• runny or stuffy nose,
• upper respiratory tract infection,
• headache,
• sinusitis,
• upset stomach or stomach pain, and
• diarrhea.

Seek medical care or call 911 at once if you have the following serious side effects:

• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms such as fast, irregular, or pounding heartbeats; fluttering in your chest; shortness of breath; and sudden dizziness, lightheartedness, or passing out;
• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors.

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

Dosage for Tresiba

The dose of Tresiba is individualized based on type of diabetes, metabolic needs, blood glucose monitoring results, and glycemic control goal.

What Drugs, Substances, or Supplements Interact with Tresiba?

Tresiba may interact with other insulin products, beta-blockers, clonidine, guanethidine, reserpine, other antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, propoxyphene, salicylates, somatostatin analogs, sulfonamide antibiotics, GLP-1 receptor agonists, DDP-4 inhibitors, SGLT-2 inhibitors, atypical antipsychotics, corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens, protease inhibitors, somatropin, sympathomimetic agents, thyroid hormones, alcohol, lithium salts, or pentamidine. Tell your doctor all medications and supplements you use.

Tresiba During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant while taking Tresiba. During pregnancy, Tresiba should only be taken if prescribed. It is unknown if Tresiba passes into breast milk. Women with diabetes who are nursing may require adjustments in insulin dose, meal plan, or both. Consult your doctor before breastfeeding.

Additional Information

Our Tresiba (insulin degludec injection) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Tresiba Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives, itching, skin rash; wheezing, tiredness, trouble breathing; feeling like you might pass out; nausea, diarrhea; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• fluid retention--weight gain, swelling in your hands or feet, feeling short of breath; or
• low potassium--leg cramps, constipation, irregular heartbeats, fluttering in your chest, increased thirst or urination, numbness or tingling, muscle weakness or limp feeling.

Common side effects may include:

• low blood sugar;
• swelling, weight gain;
• itching, rash; or
• thickening or hollowing of the skin where you injected the medicine.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Tresiba Professional Information

SIDE EFFECTS

The following adverse reactions are also discussed elsewhere:

• Hypoglycemia [see WARNINGS AND PRECAUTIONS]
• Hypoglycemia due to Medication errors [see WARNINGS AND PRECAUTIONS]
• Hypersensitivity reactions [see WARNINGS AND PRECAUTIONS]
• Hypokalemia [see WARNINGS AND PRECAUTIONS]

Clinical Trial Experience

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

The safety of TRESIBA in subjects with type 1 diabetes or type 2 diabetes was evaluated in nine trials of 6 12 month duration in adults and in one trial of 12 month duration in pediatric patients 1 year of age and older with type 1 diabetes. The cardiovascular safety of TRESIBA was evaluated in one double blinded, event driven trial of 2 year median duration in patients with type 2 diabetes at high risk of cardiovascular events [see Clinical Studies].

The data in Table 1 reflect the exposure of 1102 adults with type 1 diabetes to TRESIBA with a mean exposure duration to TRESIBA of 34 weeks in three open label trials; Study A, B and C [see Clinical Studies]. The mean age was 43 years and 1% were older than 75 years. Fifty seven percent were male, 81% were White, 2% were Black or African American and 4% were Hispanic. The mean body mass index (BMI) was 26 kg/m². The mean duration of diabetes was 18 years and the mean HbA_1c at baseline was 7.8%. A history of neuropathy, ophthalmopathy, nephropathy and cardiovascular disease at baseline was reported in 11%, 16%, 7% and 0.5% respectively. The mean eGFR at baseline was 87 mL/min/1.73 m² and 7% of the patients had an eGFR less than 60 mL/min/1.73 m².

The data in Table 2 reflect the exposure of 2713 adults with type 2 diabetes to TRESIBA with a mean exposure duration to TRESIBA of 36 weeks in six open label trials; Study D, E, F, G, H and I [see Clinical Studies]. The mean age was 58 years and 3% were older than 75 years. Fifty eight percent were male, 71% were White, 7% were Black or African American and 13% were Hispanic. The mean BMI was 30 kg/m². The mean duration of diabetes was 11 years and the mean HbA_1c at baseline was 8.3%. A history of neuropathy, ophthalmopathy, nephropathy and cardiovascular disease at baseline was reported for 14%, 10%, 6% and 0.6% of participants respectively. At baseline, the mean eGFR was 83 mL/min/1.73 m² and 9% had an eGFR less than 60 mL/min/1.73 m².

Common adverse reactions (excluding hypoglycemia) occurring in TRESIBA treated subjects during clinical trials in adult patients with type 1 diabetes mellitus and adults with type 2 diabetes mellitus are listed in Table 1 and Table 2, respectively. Common adverse reactions were defined as reactions occurring in ≥5% of the population studied. Hypoglycemia is not shown in these tables but discussed in a dedicated subsection below.

174 pediatric patients 1 year of age and older with type 1 diabetes were exposed to TRESIBA with a mean exposure to TRESIBA of 48 weeks. The mean age was 10 years: 25% were ages 1 5 years, 40% were ages 6 11 years, and 35% were ages 12 17 years. 55% were male, 78% were White, 3% were Black or African American and 4% were Hispanic. The mean body mass index (BMI) was 18.7 kg/m². The mean duration of diabetes was 3.9 years and the mean HbA_1c at baseline was 8.2%. Common adverse reactions in TRESIBA treated pediatric patients with type 1 diabetes mellitus were similar to the adverse reactions listed in Table 1.

Table 1: Adverse Reactions Occurring in ≥5% of TRESIBA Treated Adult Patients with Type 1 Diabetes Mellitus

Table 2: Adverse Reactions Occurring in ≥5% of TRESIBA Treated Adult Patients with Type 2 Diabetes Mellitus

Hypoglycemia

Hypoglycemia was the most commonly observed adverse reaction in patients treated with TRESIBA. The rates of reported hypoglycemia depend on the definition of hypoglycemia used, diabetes type, insulin dose, intensity of glucose control, background therapies, and other intrinsic and extrinsic patient factors. For these reasons, comparing rates of hypoglycemia in clinical trials for TRESIBA with the incidence of hypoglycemia for other products may be misleading and also, may not be representative of hypoglycemia rates that will occur in clinical practice.

In the open label adult clinical trials of patients with type 1 and type 2 diabetes, and in the open label pediatric clinical trial of patients with type 1 diabetes, percentages of adult and pediatric patients with type 1 diabetes randomized to TRESIBA who experienced at least one episode of hypoglycemia in clinical trials [see Clinical Studies] and adults with type 2 diabetes are shown in Tables 3 and 4, respectively. Severe hypoglycemia in the open label trials with adult patients was defined as an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.

Severe hypoglycemia in the pediatric trial was defined as an altered mental status where the child could not assist in his own care, was semiconscious or unconscious, or in a coma ± convulsions and may require parenteral therapy (glucagon or intravenous glucose). A hypoglycemia episode was defined as a severe hypoglycemia episode or an episode where a laboratory or a self measured glucose calibrated to plasma was less than 56 mg/dL or where a whole blood glucose was less than 50 mg/dL (i.e., with or without the presence of hypoglycemic symptoms).

Table 3: Percent (%) of Type 1 Diabetes Patients Experiencing at Least One Episode of Severe Hypoglycemia or Hypoglycemia^§ on TRESIBA in Open Label Adult and Pediatric Clinical Trials

Table 4: Percent (%) of Patients with Type 2 Diabetes Experiencing at Least One Episode of Severe Hypoglycemia or Hypoglycemia^§ on TRESIBA in Open Label Adult Clinical Trials

Hypersensitivity Reactions

Severe, life threatening, generalized allergy, including anaphylaxis, generalized skin reactions, angioedema, bronchospasm, hypotension, and shock have occurred with insulin, including TRESIBA and may be life threatening. Hypersensitivity (manifested with swelling of tongue and lips, diarrhea, nausea, tiredness, and itching) and urticaria were reported in 0.9% of patients treated with TRESIBA.

Lipodystrophy

Long term use of insulin, including TRESIBA, can cause lipodystrophy at the site of repeated insulin injections. Lipodystrophy includes lipohypertrophy (thickening of adipose tissue) and lipoatrophy (thinning of adipose tissue) and may affect insulin absorption [see DOSAGE AND ADMINISTRATION]. In the clinical program, lipodystrophy, lipohypertrophy, or lipoatrophy was reported in 0.3% of patients treated with TRESIBA.

Injection Site Reactions

Patients taking TRESIBA may experience injection site reactions, including injection site hematoma, pain, hemorrhage, erythema, nodules, swelling, discoloration, pruritus, warmth, and injection site mass. In the clinical program, injection site reactions occurred in 3.8% of patients treated with TRESIBA.

Weight Gain

Weight gain can occur with insulin therapy, including TRESIBA, and has been attributed to the anabolic effects of insulin. In the clinical program after 52 weeks of treatment, patients with type 1 diabetes treated with TRESIBA gained an average of 1.8 kg and patients with type 2 diabetes treated with TRESIBA gained an average of 3.0 kg.

Peripheral Edema

TRESIBA, may cause sodium retention and edema. In the clinical program, peripheral edema occurred in 0.9% of patients with type 1 diabetes mellitus and 3.0% of patients with type 2 diabetes mellitus treated with TRESIBA.

Immunogenicity

As with all therapeutic proteins, insulin administration may cause anti insulin antibodies to form. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay and may be influenced by several factors such as: assay methodology, sample handling, timing of sample collection, concomitant medication, and underlying disease. For these reasons, comparison of the incidence of antibodies to TRESIBA with the incidence of antibodies in other studies or to other products may be misleading.

In a 52 week trial of adult insulin experienced type 1 diabetes patients, 68.9% of patients who received TRESIBA were positive at baseline for anti insulin degludec antibodies and 12.3% of the patients developed anti insulin degludec antibodies at least once during the trial. In a 52 week trial of pediatric insulin experienced type 1 diabetes patients, 84.1% of patients who received TRESIBA were positive at baseline for anti insulin degludec antibodies and 5.8% of patients developed anti insulin degludec antibodies at least once during the trial. In a 52 week trial of adult insulin naïve type 2 diabetes patients, 1.7% of patients who received TRESIBA were positive at baseline for anti insulin degludec antibodies and 6.2% of patients developed anti insulin degludec antibodies at least once during the trial. In these trials, between 96.7% and 99.7% of patients who were positive for anti insulin degludec antibodies were also positive for anti human insulin antibodies.

Postmarketing Experience

The following additional adverse reactions have been identified during post approval use of TRESIBA. 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.

Localized cutaneous amyloidosis at the injection site has occurred. Hyperglycemia has been reported with repeated insulin injections into areas of localized cutaneous amyloidosis; hypoglycemia has been reported with a sudden change to an unaffected injection site.

DRUG INTERACTIONS

Table 5 includes clinically significant drug interactions with TRESIBA.

Table 5: Clinically Significant Drug Interactions with TRESIBA

Read the entire FDA prescribing information for Tresiba (Insulin Degludec Injection)