Usage
- Evogliptin + Metformin is prescribed for the treatment of type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycemic control. It is indicated in patients whose blood sugar levels are not adequately managed by metformin alone or as an alternative to separate administration of evogliptin and metformin.
- Pharmacological Classification: Antidiabetic, Dipeptidyl Peptidase-4 (DPP-4) inhibitor in combination with a biguanide.
- Mechanism of Action: Evogliptin works by inhibiting the enzyme DPP-4, which increases the levels of incretin hormones like GLP-1 and GIP. These hormones stimulate insulin release and suppress glucagon secretion, leading to improved blood glucose control. Metformin primarily works by decreasing hepatic glucose production and improving insulin sensitivity.
Alternate Names
- While “Evogliptin + Metformin” is the generic name, the combination itself does not appear to have other generic names. Evogliptin is sometimes referred to as Evodin.
- Brand Names: This combination is marketed under various brand names such as Valera M and Suganon M.
How It Works
- Pharmacodynamics: Evogliptin increases incretin hormone levels (GLP-1 and GIP), leading to increased glucose-dependent insulin secretion and reduced glucagon release. Metformin decreases hepatic glucose production, increases peripheral glucose uptake, and improves insulin sensitivity.
- Pharmacokinetics:
- Evogliptin: Orally administered evogliptin reaches maximum plasma concentration (Cmax) within 3–5.5 hours. It has an oral bioavailability of over 50%. Food does not affect its absorption. Steady state is achieved by the third day of administration. Evogliptin is primarily metabolized by CYP3A4 and approximately 46.1% of the dose is excreted in urine and 42.8% in feces. It has an elimination half-life of 32.5 to 39.8 hours.
- Metformin: Metformin is readily absorbed from the gastrointestinal tract, though bioavailability is approximately 50-60%. It does not bind to plasma proteins. Metformin is not metabolized in the liver. It is excreted unchanged primarily by the kidneys. Elimination half-life is approximately 1.5 to 4.5 hours.
- Mode of Action: Evogliptin competitively binds to and inhibits DPP-4, preventing the breakdown of incretins. Metformin’s mechanisms are complex and not fully elucidated but involve activation of AMP-activated protein kinase (AMPK).
- Receptor binding, enzyme inhibition, or neurotransmitter modulation: Evogliptin exhibits selective inhibition of the DPP-4 enzyme. Metformin interacts with mitochondrial respiratory-chain complex 1.
- Elimination pathways: Evogliptin is eliminated through both renal and hepatic pathways, while metformin is excreted unchanged mainly by the kidneys.
Dosage
Standard Dosage
Adults:
- The standard dose is Evogliptin 5 mg + Metformin 500-1000mg once daily. The maximum dose of Evogliptin is 5 mg/day and Metformin is 2000mg/day.
- The fixed-dose combination tablets should be administered with food to minimize the gastrointestinal side effects of metformin.
Children:
- The safety and efficacy of evogliptin + metformin have not been established in pediatric patients.
Special Cases:
- Elderly Patients: Use with caution, monitor renal function, and consider dosage adjustment as needed.
- Patients with Renal Impairment: Evogliptin does not generally require dose adjustment. Metformin dosage should be reduced or avoided based on the creatinine clearance level. Contraindicated in end-stage renal disease.
- Patients with Hepatic Dysfunction: Evogliptin does not generally require dose adjustment in mild to moderate impairment, but its safety and effectiveness haven’t been studied in those with severe hepatic impairment. Metformin should be used with caution in those with moderate hepatic impairment and is contraindicated in severe impairment.
- Patients with Comorbid Conditions: In patients with heart failure (NYHA Class I), evogliptin + metformin should be used with caution. It is not recommended in patients with NYHA Class II-IV heart failure.
Clinical Use Cases
- This combination is not typically used in clinical settings such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
- Dosage adjustments are primarily based on renal function and the patient’s response to therapy.
Side Effects
Common Side Effects
- Indigestion, nausea, vomiting, diarrhea, abdominal pain, headache, nasopharyngitis, and joint pain.
Rare but Serious Side Effects
- Acute pancreatitis, severe hypersensitivity reactions, lactic acidosis (metformin), bullous pemphigoid, and Stevens-Johnson syndrome.
Long-Term Effects
- Long-term side effects are not specifically documented but may include those of the individual components.
Adverse Drug Reactions (ADR)
- Angioedema, pancreatitis, and severe skin reactions require immediate attention. Lactic acidosis, though rare, requires urgent medical intervention.
Contraindications
- Hypersensitivity to evogliptin or metformin.
- Type 1 diabetes, diabetic ketoacidosis, severe ketosis, diabetic coma, or pre-coma.
- Severe renal impairment or end-stage renal disease.
- Severe hepatic impairment.
- Conditions that may predispose to lactic acidosis (e.g., acute myocardial infarction, severe respiratory failure, hypoperfusion, sepsis, dehydration).
Drug Interactions
- CYP3A4 Inhibitors: (e.g., clarithromycin, ketoconazole) may increase evogliptin exposure, requiring caution.
- CYP3A4 Inducers: (e.g., rifampicin) may decrease evogliptin exposure, potentially reducing efficacy.
- Alcohol: Concomitant alcohol use with metformin increases the risk of lactic acidosis.
- Iodinated contrast media: Metformin should be temporarily discontinued before and after receiving iodinated contrast media.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: There is limited data on the use of evogliptin in pregnant women. Use only if the potential benefit outweighs the potential risk to the fetus. Metformin crosses the placenta.
- Breastfeeding: Evogliptin is contraindicated during lactation as it is present in rat milk. Metformin is present in human milk.
Drug Profile Summary
- Mechanism of Action: DPP-4 inhibition (evogliptin) and reduction of hepatic glucose production/improved insulin sensitivity (metformin).
- Side Effects: Indigestion, nausea, diarrhea, nasopharyngitis, joint pain, lactic acidosis (metformin), pancreatitis, severe hypersensitivity reactions.
- Contraindications: Hypersensitivity, type 1 diabetes, diabetic ketoacidosis, severe renal/hepatic impairment.
- Drug Interactions: CYP3A4 inhibitors/inducers, alcohol, iodinated contrast media.
- Pregnancy & Breastfeeding: Caution in pregnancy; contraindicated during breastfeeding.
- Dosage: Evogliptin 5mg + Metformin 500-1000mg once daily.
- Monitoring Parameters: HbA1c, fasting and postprandial blood glucose, renal function, signs of lactic acidosis or pancreatitis.
Popular Combinations
- Evogliptin + Metformin is itself a popular combination. Other antidiabetic agents, such as SGLT2 inhibitors or insulin, might be added if glycemic control is not achieved with Evogliptin + Metformin.
Precautions
- Assess renal and hepatic function before and during treatment, especially in elderly patients.
- Patients should be educated about the signs and symptoms of lactic acidosis and pancreatitis.
- Caution should be exercised in patients with heart failure.
FAQs (Frequently Asked Questions)
A: The standard recommended dosage for adults is Evogliptin 5 mg + Metformin 500-1000mg taken orally once daily with food.
A: No, Evogliptin + Metformin is contraindicated in patients with type 1 diabetes. It is specifically indicated for type 2 diabetes mellitus.
A: The most common side effects include gastrointestinal issues like nausea, vomiting, diarrhea, and indigestion, as well as nasopharyngitis and joint pain.
Q4: Are there any serious side effects I should be aware of?
A: While rare, serious side effects like acute pancreatitis and lactic acidosis (associated with metformin) can occur. Patients should be educated about the symptoms of these conditions.
Q5: How should I adjust the dose in patients with renal impairment?
A: Evogliptin typically doesn’t require dosage adjustment, but metformin should be dose-reduced or avoided depending on the severity of the renal impairment.
Q6: Can this medication be used during pregnancy or breastfeeding?
A: Evogliptin + Metformin should be used with caution during pregnancy and is contraindicated during breastfeeding.
A: CYP3A4 inhibitors and inducers can interact with evogliptin. Alcohol can interact with metformin and increase the risk of lactic acidosis.
Q8: What should I monitor in patients taking this medication?
A: Regular monitoring of HbA1c, blood glucose levels, renal function, and signs of side effects such as lactic acidosis or pancreatitis are essential.
A: No, the fixed-dose combination tablets should be swallowed whole and not crushed, chewed or split.
