Usage
- Evogliptin is prescribed for the treatment of type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycemic control. It can be used as monotherapy or in combination with metformin.
- Pharmacological Classification: Dipeptidyl peptidase-4 (DPP-4) inhibitor, Antidiabetic agent.
- Mechanism of Action: Evogliptin works by inhibiting the DPP-4 enzyme, which is responsible for breaking down incretin hormones like GLP-1 and GIP. These hormones play a crucial role in regulating blood glucose levels by stimulating insulin release and suppressing glucagon secretion. By inhibiting DPP-4, Evogliptin increases the levels of active incretin hormones, leading to improved glycemic control.
Alternate Names
- Evogliptin Tartrate.
- Brand Names: Valera, Evodin, Suganon, Gojeku.
How It Works
- Pharmacodynamics: Evogliptin selectively inhibits DPP-4, leading to increased levels of active GLP-1 and GIP. This results in enhanced glucose-dependent insulin secretion, suppressed glucagon release, and ultimately, reduced blood glucose levels.
- Pharmacokinetics:
- Absorption: Administered orally, Evogliptin reaches peak plasma concentrations within a few hours. Food intake does not significantly affect its absorption.
- Metabolism: Primarily metabolized by CYP3A4.
- Elimination: Approximately 46.1% is excreted in urine and 42.8% in feces, including both the unchanged drug and its metabolites.
- Mode of Action: Evogliptin binds to and inhibits the DPP-4 enzyme, preventing the degradation of incretin hormones.
- Receptor Binding/Enzyme Inhibition: Inhibits DPP-4 enzyme activity, with an IC50 of 0.980 nM and a Ki of 0.525 nM. Does not significantly interact with DPP-8 and DPP-9. Not an inhibitor of or inducer of major CYP enzymes. It is a P-gp substrate and a weak BCRP substrate, but it doesn’t inhibit these transporters. It doesn’t interact with OAT1, OAT3, OCT2, OATP1B1, and OATP1B3.
- Elimination Pathways: Renal and hepatic excretion.
Dosage
Standard Dosage
Adults:
- 5 mg orally once daily, with or without food.
- Maximum daily dose: 5 mg.
Children:
- Safety and efficacy in pediatric patients have not been established.
Special Cases:
- Elderly Patients: Administer with caution due to potential decreased hepatic and renal function. Monitor patient condition closely.
- Patients with Renal Impairment: Administer cautiously, as increased blood concentrations of Evogliptin may occur in patients with moderate to severe renal impairment.
- Patients with Hepatic Dysfunction: Dose adjustment is not needed in patients with mild to moderate hepatic impairment.
- Patients with Comorbid Conditions: Use with caution in patients with heart failure (NYHA Class I), a history of pancreatitis, and other relevant conditions. Dosage adjustments might be needed.
Clinical Use Cases
- The provided sources do not offer specific dosage recommendations for Evogliptin in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary indication is for chronic management of type 2 diabetes.
Dosage Adjustments
- Dose adjustments may be necessary in patients with renal/hepatic impairment and in those taking concomitant medications that interact with Evogliptin, such as CYP3A4 inhibitors (e.g., clarithromycin) or inducers (e.g., rifampicin).
Side Effects
Common Side Effects:
- Indigestion
- Diarrhea
- Nasopharyngitis (cold)
- Gastritis
- Joint pain
- Headache
- Upper respiratory tract infections
Rare but Serious Side Effects:
- Pancreatitis
- Severe joint pain
- Allergic reactions (e.g., angioedema)
- Hypoglycemia (especially when combined with other antidiabetic medications)
- Lactic Acidosis (with metformin combination)
Long-Term Effects:
- Long-term effects of Evogliptin are still under investigation. Monitoring for potential complications like pancreatitis and renal function changes is important.
Adverse Drug Reactions (ADR):
- Angioedema
- Acute pancreatitis
- Severe hypersensitivity reactions
Contraindications
- Hypersensitivity to Evogliptin or any of its components
- Type 1 diabetes mellitus
- Diabetic ketoacidosis
- Severe ketosis, diabetic coma or pre-coma
- Pregnancy and lactation
- NYHA Class II-IV heart failure
Drug Interactions
- CYP3A4 Inhibitors (e.g., clarithromycin): May increase Evogliptin exposure.
- CYP3A4 Inducers (e.g., rifampicin): May decrease Evogliptin exposure.
- Other Antidiabetic Medications (e.g., sulfonylureas, insulin): Increased risk of hypoglycemia.
- Metformin: No clinically significant interaction.
- Alcohol: Potential interaction is unknown. Alcohol may worsen side effects such as lactic acidosis (especially when combined with metformin) and hypoglycemia.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Not established. Use is not recommended due to potential fetal risks. Animal studies show placental transfer.
- Breastfeeding: Use is not recommended, as Evogliptin may be excreted in breast milk. Animal studies confirm secretion in milk.
Drug Profile Summary
- Mechanism of Action: DPP-4 inhibitor, increasing incretin hormone levels.
- Side Effects: Indigestion, diarrhea, nasopharyngitis, gastritis, joint pain, headache, pancreatitis (rare), hypoglycemia (with other antidiabetics).
- Contraindications: Hypersensitivity, type 1 diabetes, diabetic ketoacidosis, pregnancy, breastfeeding, NYHA Class II-IV heart failure.
- Drug Interactions: CYP3A4 inhibitors/inducers, other antidiabetics.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: 5 mg orally once daily.
- Monitoring Parameters: Blood glucose levels, HbA1c, renal function, liver function tests, signs of pancreatitis.
Popular Combinations
- Metformin: Commonly used in combination with Evogliptin for enhanced glycemic control in type 2 diabetes.
Precautions
- Screen for allergies, heart failure, renal/hepatic dysfunction, and history of pancreatitis.
- Pregnant Women: Avoid use.
- Breastfeeding Mothers: Avoid use.
- Children & Elderly: Not recommended for children. Use with caution in the elderly.
- Lifestyle Considerations: Advise patients on diet, exercise, and alcohol consumption.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Evogliptin?
A: The recommended dosage for adults is 5 mg orally once daily, with or without food. Not recommended for children.
Q2: How does Evogliptin work?
A: It inhibits DPP-4, increasing incretin hormone levels, which in turn enhances insulin release and suppresses glucagon.
Q3: What are the common side effects?
A: Indigestion, diarrhea, nasopharyngitis, gastritis, joint pain, and headache are common.
Q4: Can Evogliptin be used during pregnancy?
A: No, it’s contraindicated during pregnancy and breastfeeding.
Q5: What are the serious side effects to watch for?
A: Pancreatitis, severe allergic reactions, and hypoglycemia (especially when used with other antidiabetic agents) are rare but serious side effects.
Q6: Does Evogliptin interact with other medications?
A: Yes, it can interact with CYP3A4 inhibitors (e.g., clarithromycin), CYP3A4 inducers (e.g., rifampicin), and other antidiabetic medications.
Q7: What should patients be advised about lifestyle modifications?
A: Patients should be advised on diet, exercise, and limiting alcohol intake. They should also be educated on how to monitor their blood glucose levels.
Q8: Can Evogliptin be used in patients with renal impairment?
A: It should be used with caution in patients with renal impairment. Dose adjustments may be necessary depending on the severity of impairment.
Q9: What is the maximum dose of Evogliptin?
A: The maximum recommended dose is 5 mg per day.
Q10: What are the contraindications for Evogliptin use?
A: Contraindications include hypersensitivity to Evogliptin, type 1 diabetes, diabetic ketoacidosis, pregnancy, breastfeeding, and NYHA Class II-IV heart failure.
