Teneligliptin

Usage

• Teneligliptin is prescribed for Type 2 diabetes mellitus in adults. It is used as monotherapy when metformin is contraindicated or not tolerated, or in combination with other antidiabetic agents (e.g., metformin, pioglitazone, sulfonylureas, glinides, α-glucosidase inhibitors) and/or insulin when these, along with diet and exercise, do not provide adequate glycemic control.
• Pharmacological Classification: Dipeptidyl peptidase-4 (DPP-4) inhibitor, Antidiabetic agent.
• Mechanism of Action: Teneligliptin works by inhibiting the enzyme DPP-4. This enzyme breaks down incretin hormones like GLP-1 and GIP, which play a crucial role in glucose regulation by increasing insulin release and decreasing glucagon secretion in a glucose-dependent manner. By inhibiting DPP-4, teneligliptin increases and prolongs the action of these incretin hormones, thereby improving glycemic control.

Alternate Names

• It is known as Teneligliptin Hydrobromide Hydrate in some contexts.
• Brand Names: Tilyptin, Glipten, Ten-20, Olymprix, TENEBLU, Tenelisign, Olymprix M (combination with Metformin).

How It Works

• Pharmacodynamics: Teneligliptin primarily exerts its glucose-lowering effect by inhibiting DPP-4. This leads to increased and prolonged levels of active incretin hormones, GLP-1 and GIP. These hormones stimulate glucose-dependent insulin secretion from pancreatic beta-cells and suppress glucagon secretion from alpha-cells. The glucose-dependent nature of this mechanism minimizes the risk of hypoglycemia.
• Pharmacokinetics: Teneligliptin is rapidly absorbed after oral administration, reaching peak plasma concentrations in about 1-2 hours. It is primarily metabolized by CYP3A4 and FMO3 enzymes in the liver, with minor contributions from CYP2D6 and FMO1. The metabolites are eliminated via both renal and hepatic routes. Renal impairment does not require dose adjustment.
• Mode of Action: Teneligliptin competitively binds to and inhibits the active site of the DPP-4 enzyme, preventing the cleavage of incretin hormones.
• Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Teneligliptin specifically inhibits the DPP-4 enzyme.
• Elimination Pathways: Teneligliptin is eliminated through both renal and hepatic pathways following metabolism primarily by CYP3A4 and FMO3.

Dosage

Standard Dosage

Adults:

• Initial dose: 20 mg orally once daily, with or without food.
• Maintenance dose: If the initial dose is insufficient, it can be increased to a maximum of 40 mg orally once daily.

Children:

• The safety and efficacy of teneligliptin have not been established in pediatric patients. It is not recommended for use in this population.

Special Cases:

• Elderly Patients: Dose adjustment is generally not required. However, caution is advised due to potential age-related physiological decline.
• Patients with Renal Impairment: No dose adjustment is necessary.
• Patients with Hepatic Dysfunction: Dose adjustment is not required for mild to moderate hepatic impairment. Use with caution in patients with severe hepatic impairment as safety and efficacy have not been established.
• Patients with Comorbid Conditions: Exercise caution in patients with congestive heart failure, history of arrhythmia, bradycardia, low serum potassium, QT prolongation, or those taking other medications affecting QT interval. Caution is also needed in patients with pituitary/adrenal insufficiency, bowel obstruction, or excessive alcohol intake.

Clinical Use Cases

Teneligliptin is not indicated for use in clinical settings such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its usage is specifically for managing type 2 diabetes mellitus.

Dosage Adjustments

Dose adjustments are based primarily on efficacy and tolerability. If 20 mg/day is insufficient to achieve target glycemic control, the dose can be increased to a maximum of 40 mg/day.

Side Effects

Common Side Effects:

• Hypoglycemia (especially when combined with sulfonylureas or insulin)
• Constipation
• Headache
• Upper respiratory tract infection
• Nasopharyngitis
• Gastrointestinal symptoms (abdominal pain, nausea, diarrhea)
• Fatigue
• Skin rashes or itching

Rare but Serious Side Effects:

• Acute pancreatitis
• Hepatic dysfunction (elevated liver enzymes)
• Allergic reactions (exanthematous drug eruptions, pruritic maculopapular rashes)
• Kidney problems (rare)
• Intestinal obstruction (rare)
• Bullous pemphigoid
• Interstitial pneumonia

Long-Term Effects:

• Potential long-term effects are not fully characterized but may include those related to chronic hyperglycemia if diabetes is not adequately managed.

Adverse Drug Reactions (ADR):

• Angioedema, Stevens-Johnson syndrome, bullous pemphigoid.

Contraindications

• Hypersensitivity to teneligliptin or any component of the formulation.
• Type 1 diabetes mellitus.
• Diabetic ketoacidosis or history of diabetic coma.
• Severe infections, severe trauma, or major surgery (insulin therapy is preferred).
• Severe hepatic impairment.

Drug Interactions

• Medications that enhance blood glucose-lowering effects: Sulfonylureas, insulin, biguanides, beta-blockers, MAO inhibitors, salicylic acid. Dosage adjustments of these medications may be needed.
• Medications that reduce blood glucose-lowering effects: Corticosteroids, thyroid hormones.
• Ketoconazole: Increases teneligliptin exposure.
• CYP3A4 inducers (e.g., rifampin): May decrease teneligliptin effectiveness.
• Alcohol: Increases the risk of lactic acidosis, especially with metformin co-administration.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: There is limited data. Use only if the potential benefit justifies the potential risk to the fetus.
• Fetal Risks/Teratogenicity: Not well established, but animal studies show potential adverse effects on fertility and fetal development.
• Breastfeeding: Teneligliptin is excreted in breast milk (in animals). Breastfeeding is not recommended.

Drug Profile Summary

• Mechanism of Action: DPP-4 inhibitor, increases and prolongs incretin hormone levels, leading to glucose-dependent insulin release and reduced glucagon secretion.
• Side Effects: Hypoglycemia, constipation, headache, upper respiratory tract infection, nasopharyngitis, gastrointestinal issues, fatigue, skin reactions. Rarely pancreatitis, liver dysfunction, allergic reactions, kidney problems, intestinal obstruction.
• Contraindications: Hypersensitivity, type 1 diabetes, diabetic ketoacidosis, severe infections/trauma/surgery, severe hepatic impairment.
• Drug Interactions: Sulfonylureas, insulin, beta-blockers, MAOIs, corticosteroids, thyroid hormones, ketoconazole, alcohol.
• Pregnancy & Breastfeeding: Not recommended.
• Dosage: Adults: 20 mg once daily, increased to 40 mg if needed. Not for pediatric use.
• Monitoring Parameters: Plasma glucose, HbA1c, liver function tests, renal function (if indicated), signs/symptoms of pancreatitis.

Popular Combinations

• Teneligliptin + Metformin: Offers synergistic glucose-lowering effects.

Precautions

• General Precautions: Monitor for hypoglycemia, liver function, renal function (if indicated), and gastrointestinal issues. Assess for history of pancreatitis, heart conditions, and allergies.
• Specific Populations: Avoid use in pregnancy and breastfeeding. Use with caution in the elderly and those with hepatic impairment. Not for pediatric use.
• Lifestyle Considerations: Moderate alcohol consumption.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Teneligliptin?

A: The recommended starting dose is 20 mg once daily. If this is not effective, the dose can be increased to 40 mg once daily.

Q2: How does Teneligliptin differ from other DPP-4 inhibitors?

A: While the core mechanism is shared, teneligliptin’s specific pharmacokinetic and pharmacodynamic properties may influence its efficacy and side effect profile compared to other DPP-4 inhibitors. Clinical experience and direct comparison studies provide further differentiation.

Q3: Can Teneligliptin be used in patients with renal impairment?

A: Yes, unlike many other antidiabetic medications, teneligliptin does not require dose adjustment in patients with renal impairment, including end-stage renal disease.

Q4: Does Teneligliptin cause weight gain?

A: Teneligliptin is considered weight-neutral and is not associated with significant weight gain or loss.

Q5: What are the most common side effects of Teneligliptin?

A: The most frequently reported side effects are hypoglycemia and constipation.

Q6: Can Teneligliptin be used in patients with liver disease?

A: Teneligliptin should be used with caution in patients with severe hepatic impairment. Dose adjustment is not required for mild to moderate hepatic impairment, but close monitoring is necessary.

Q7: Is Teneligliptin safe to use during pregnancy?

A: The safety of Teneligliptin during pregnancy has not been established. Its use is generally avoided, and if considered, should only be when the potential benefit outweighs the potential risk to the fetus.

Q8: What should be done if a patient misses a dose of Teneligliptin?

A: If a dose is missed, take it as soon as remembered, unless it is close to the next scheduled dose. Do not double the dose.

Q9: Can Teneligliptin be combined with other diabetes medications?

A: Yes, Teneligliptin can be used in combination with other oral antidiabetic agents like metformin, sulfonylureas, thiazolidinediones, and even with insulin. However, dose adjustments of other agents, especially sulfonylureas and insulin, might be needed to prevent hypoglycemia.

Q10: What are the serious side effects of Teneligliptin that require attention?

A: Rare but serious side effects include acute pancreatitis, severe allergic reactions (angioedema, Stevens-Johnson Syndrome), bullous pemphigoid, and significant hepatic dysfunction. Any sign or symptom suggesting these conditions requires immediate medical attention.