Skip to Content

Linagliptin

Medically reviewed by Drugs.com. Last updated on July 1, 2020.

Pronunciation

(lin a GLIP tin)

Index Terms

  • BI-1356
  • Trajenta

Dosage Forms

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

Tablet, Oral:

Tradjenta: 5 mg [contains corn starch]

Brand Names: U.S.

  • Tradjenta

Pharmacologic Category

  • Antidiabetic Agent, Dipeptidyl Peptidase 4 (DPP-4) Inhibitor

Pharmacology

Linagliptin inhibits dipeptidyl peptidase 4 (DPP-4) enzyme resulting in prolonged active incretin levels. Incretin hormones (eg, glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]) regulate glucose homeostasis by increasing insulin synthesis and release from pancreatic beta cells and decreasing glucagon secretion from pancreatic alpha cells. Decreased glucagon secretion results in decreased hepatic glucose production. Under normal physiologic circumstances, incretin hormones are released by the intestine throughout the day and levels are increased in response to a meal; incretin hormones are rapidly inactivated by the DPP-4 enzyme.

Distribution

Extensive

Metabolism

Not extensively metabolized

Excretion

80% feces unchanged; 5% urine unchanged

Time to Peak

1.5 hours

Half-Life Elimination

~11 hours; Terminal (DPP-4 saturable binding): ~200 hours.

Protein Binding

70% to 80%; concentration dependent

Use: Labeled Indications

Diabetes mellitus, type 2, treatment: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes as monotherapy or in combination with other antidiabetic agents.

Contraindications

Hypersensitivity (eg, anaphylaxis, angioedema, exfoliative skin conditions, urticaria, or bronchial hyperreactivity) to linagliptin or any component of the formulation

Canadian labeling: Additional contraindications: Use in type 1 diabetes mellitus or diabetic ketoacidosis

Dosing: Adult

Note: Due to lack of additive glycemic benefit, avoid concomitant use of a glucagon-like peptide-1 receptor agonist (ADA/EASD [Davies 2018]). May require a dose reduction of insulin and/or insulin secretagogues to avoid hypoglycemia.

Diabetes mellitus, type 2, treatment:

Note: May be used as an adjunctive agent or alternative monotherapy for patients who fail initial therapy with lifestyle intervention and metformin or who cannot take metformin. May be preferred in patients who are close to glycemic goals when avoidance of hypoglycemia and/or weight gain is desirable; use has not been associated with improved or worsened cardiovascular or renal outcomes (AACE/ACE [Garber 2020]; ADA 2020; Rosenstock 2019).

Oral: 5 mg once daily.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Administration

Oral: May be administered with or without food.

Dietary Considerations

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

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F).

Drug Interactions

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

Androgens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: Dipeptidyl Peptidase-IV Inhibitors may enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Monitor therapy

Antihepaciviral Combination Products: May increase the serum concentration of LinaGLIPtin. Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of LinaGLIPtin. Management: Strongly consider using an alternative to any strong CYP3A4 inducer in patients who are being treated with linagliptin. If this combination is used, monitor patients closely for evidence of reduced linagliptin effectiveness. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to concomitant therapy when possible. If concomitant therapy cannot be avoided, monitor for reduced clinical effects of the CYP3A4 substrate. Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

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

Insulins: 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

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Maitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

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

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

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of LinaGLIPtin. Management: Strongly consider using an alternative to any P-glycoprotein inducer in patients who are being treated with linagliptin. If this combination is used, monitor patients closely for evidence of reduced linagliptin effectiveness. Consider therapy modification

Prothionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy

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

Ritonavir: May increase the serum concentration of LinaGLIPtin. Monitor therapy

Salicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

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

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Sulfonylureas: Dipeptidyl Peptidase-IV Inhibitors may enhance the hypoglycemic effect of Sulfonylureas. Management: Consider a decrease in sulfonylurea dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Consider therapy modification

Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Incidences may include use in combination therapy regimens.

1% to 10%:

Endocrine & metabolic: Hypoglycemia (7%), increased uric acid (3%)

Gastrointestinal: Increased serum lipase (8%; >3x upper limit of normal)

Respiratory: Nasopharyngitis (7%), cough (2%)

Frequency not defined:

Dermatologic: Urticaria

Neuromuscular & skeletal: Myalgia

Respiratory: Bronchoconstriction

Postmarketing: Acute pancreatitis, anaphylaxis, angioedema, bullous pemphigoid, exfoliation of skin, oral mucosa ulcer, rhabdomyolysis, severe arthralgia, severe hypersensitivity, skin rash, stomatitis

Warnings/Precautions

Concerns related to adverse effects:

• Arthralgia: Severe and disabling arthralgia has been reported with DPP-4 inhibitor use; onset may occur within one day to years after treatment initiation and may resolve with discontinuation of therapy. Some patients may experience a recurrence of symptoms if DPP-4 inhibitor therapy resumed.

• Bullous pemphigoid: DPP-4 inhibitor use has been associated with development of bullous pemphigoid; cases have typically resolved with topical or systemic immunosuppressive therapy and discontinuation of DPP-4 inhibitor therapy. Advise patients to report development of blisters or erosions. Discontinue therapy if bullous pemphigoid is suspected and consider referral to a dermatologist.

• Hypersensitivity reactions: Rare hypersensitivity reactions (including anaphylaxis, angioedema, and exfoliative skin conditions) have been reported in patients treated with linagliptin; events have generally been noted within the first 3 months of therapy and may occur with the initial dose. Discontinue if signs/symptoms of hypersensitivity reactions occur. Use with caution if patient has experienced angioedema with other DPP-4 inhibitor use.

• Pancreatitis: Cases of acute pancreatitis, including fatalities, have been reported with use. Monitor for signs/symptoms of pancreatitis; discontinue use immediately if pancreatitis is suspected and initiate appropriate management. Use with caution in patients with a history of pancreatitis as it is not known if this population is at greater risk.

Disease-related concerns:

• Bariatric surgery:

Altered absorption: Absorption may be altered given the anatomic and transit changes created by gastric bypass and sleeve gastrectomy surgery (Mechanick 2013; Melissas 2013).

Glucagon-like peptide-1 exposure and therapeutic efficacy: Closely monitor for signs and symptoms of pancreatitis; gastric bypass and sleeve gastrectomy may increase endogenous secretion of glucagon-like peptide-1 (Korner 2009; Peterli 2012). A single-dose, placebo-controlled study evaluated short-term therapy (4 weeks) with sitagliptin in gastric bypass patients having persistent or recurrent type 2 diabetes and found it to be well tolerated and provided a small but significant reduction in postprandial blood glucose (Shah 2018).

• Cardiovascular disease: In cardiovascular outcome trials of patients with type 2 diabetes and atherosclerotic cardiovascular disease, treatment with other DPP-4 inhibitors has been associated with heart failure. However, in a randomized, double-blind, placebo-controlled trial of patients with type 2 diabetes mellitus and high cardiovascular and renal risks, the occurrence of the primary composite cardiovascular outcome (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke) with linagliptin was found to be noninferior to placebo. In addition, the rate of hospitalization for heart failure did not differ from placebo, including in patients with preexisting heart failure. Median follow-up was 2.2 years (McGuire 2018; Rosenstock 2019). The ADA suggests DPP-4 inhibitors (except saxagliptin) may be considered in patients with heart failure (ADA 2020).

Other warnings/precautions:

• Appropriate use: Not indicated for use in patients with type 1 diabetes mellitus or with diabetic ketoacidosis.

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

Monitoring Parameters

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 2020]), serum glucose; signs/symptoms of pancreatitis; signs/symptoms of heart failure.

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 HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2020; Blumer 2013).

Agents other than linagliptin are currently recommended to treat diabetes mellitus in pregnancy (ADA 2020).

Patient Education

What is this drug used for?

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

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Sore throat

• Stuffy nose

• Runny nose

• Cough

• Diarrhea

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Low blood sugar like dizziness, headache, fatigue, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating

• Pancreatitis like severe abdominal pain, severe back pain, severe nausea, or vomiting

• Heart problems like cough or shortness of breath that is new or worse, swelling of the ankles or legs, abnormal heartbeat, weight gain of more than five pounds in 24 hours, dizziness, or passing out

• Skin blisters

• Skin breakdown

• Persistent joint pain

• Severe joint pain

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, 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 limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.