Metformin + Teneligliptin

Usage

• Metformin + Teneligliptin is prescribed for the treatment of Type 2 Diabetes Mellitus in adults, specifically when diet and exercise alone or treatment with either Metformin or Teneligliptin monotherapy does not provide adequate glycemic control. It is also indicated when glycemic control is not achieved with 1000 mg of Metformin monotherapy, especially in obese patients with Type 2 diabetes.

• Pharmacological Classification: Oral Antihyperglycemic, Biguanide (Metformin) and Dipeptidyl Peptidase-4 (DPP-4) Inhibitor (Teneligliptin).

• Mechanism of Action: This combination medication works through two distinct mechanisms to lower blood sugar levels. Metformin decreases hepatic glucose production, reduces intestinal glucose absorption, and improves insulin sensitivity in peripheral tissues. Teneligliptin inhibits the DPP-4 enzyme, which leads to increased levels of incretin hormones like GLP-1 and GIP. These hormones stimulate insulin secretion from the pancreas when blood glucose levels are high and suppress glucagon secretion.

Alternate Names

• While “Metformin + Teneligliptin” represents the generic name, various pharmaceutical companies market this combination under different brand names.
• Brand Names: Examples include Ten 20-M, Olymprix M, TENEBLU-M, and others, depending on the region and manufacturer.

How It Works

• Pharmacodynamics: Metformin improves insulin sensitivity, decreases hepatic glucose production, and reduces intestinal glucose absorption. Teneligliptin prolongs the activity of incretin hormones (GLP-1 and GIP), leading to glucose-dependent insulin secretion and suppression of glucagon release.

• Pharmacokinetics:

  • Absorption: Both Metformin and Teneligliptin are orally absorbed. Metformin’s absorption is enhanced when taken with food.
  • Metabolism: Metformin is not metabolized. Teneligliptin is primarily metabolized by CYP3A4, with minor contributions from other CYP enzymes.
  • Elimination: Metformin is excreted unchanged in the urine. Teneligliptin is excreted through both renal and hepatic pathways.

• Mode of Action: Metformin acts by activating AMP-activated protein kinase (AMPK), leading to the observed effects on glucose metabolism. Teneligliptin competitively inhibits DPP-4, preventing the breakdown of incretin hormones and thus increasing their circulating levels.

• Receptor Binding/Enzyme Inhibition: Teneligliptin is a DPP-4 enzyme inhibitor. Metformin does not directly bind to receptors but acts through AMPK activation.

• Elimination Pathways: Metformin is renally excreted. Teneligliptin is excreted through renal and hepatic pathways, with CYP3A4 playing a role in its metabolism.

Dosage

Standard Dosage

Adults:

• The initial dose is typically Metformin 500 mg + Teneligliptin 20 mg once daily, taken orally with food.
• The dosage can be increased to a maximum of Metformin 2000 mg + Teneligliptin 40 mg daily, based on glycemic control and tolerability. Adjustments should be made at intervals of 2-4 weeks.

Children:

• This combination is not recommended for patients under 18 years of age. Safety and efficacy have not been established in pediatric populations.

Special Cases:

• Elderly Patients: Renal function should be monitored regularly in elderly patients, as Metformin is excreted renally. Dosage adjustments may be needed based on renal function.
• Patients with Renal Impairment: Metformin + Teneligliptin is contraindicated in patients with severe renal impairment (e.g., serum creatinine levels ≥1.5 mg/dL in men, ≥1.4 mg/dL in women, or abnormal creatinine clearance). Caution and dose adjustments are required in mild to moderate renal impairment.
• Patients with Hepatic Dysfunction: Teneligliptin should be used with caution in patients with hepatic impairment. Metformin should not be used in patients with severe liver disease.
• Patients with Comorbid Conditions: Use with caution in patients with heart failure, a history of lactic acidosis, or those at risk for hypoglycemia.

Clinical Use Cases

Metformin + Teneligliptin is specifically indicated for the chronic management of Type 2 diabetes mellitus. It is not typically used in acute settings like intubation, surgical procedures, mechanical ventilation, ICU care, or emergency situations. Insulin is generally preferred for managing blood glucose in these acute settings.

Dosage Adjustments

Dose adjustments are based on individual patient factors, such as glycemic control, renal function, hepatic function, and potential drug interactions.

Side Effects

Common Side Effects

• Nausea
• Vomiting
• Diarrhea
• Stomach ache
• Headache
• Hypoglycemia (especially when combined with other antidiabetic drugs)
• Constipation
• Loss of appetite
• Bloating
• Flatulence

Rare but Serious Side Effects

• Lactic acidosis (a buildup of lactic acid in the blood) - requires immediate medical attention.
• Severe hypoglycemia

Long-Term Effects

• Vitamin B12 deficiency (with long-term Metformin use)

Adverse Drug Reactions (ADR)

• Lactic Acidosis
• Severe hypoglycemia
• Angioedema (rare)

Contraindications

• Hypersensitivity to Metformin or Teneligliptin
• Type 1 diabetes mellitus
• Severe renal impairment
• Diabetic ketoacidosis
• Severe infections, trauma, or major surgery
• Acute or chronic metabolic acidosis
• History of lactic acidosis
• Heart failure (NYHA class III-IV)

Drug Interactions

• Alcohol (increases risk of lactic acidosis and hypoglycemia)
• Cationic drugs eliminated by renal tubular secretion (e.g., amiloride, digoxin, morphine, procainamide, quinidine, ranitidine, vancomycin) – may decrease Metformin elimination.
• Rifampicin, Tetracycline, Clarithromycin (may reduce Metformin levels)
• Fluconazole (may increase Teneligliptin levels)
• Other oral antidiabetic agents (may increase the risk of hypoglycemia)
• Medications that induce hyperglycemia (e.g., corticosteroids, thiazides, thyroid hormones) – may require dose adjustment of Metformin + Teneligliptin.
• CYP3A4 inhibitors (e.g., ketoconazole) may increase Teneligliptin exposure.

Pregnancy and Breastfeeding

• Pregnancy: Metformin + Teneligliptin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Insulin is generally preferred for glycemic control during pregnancy.
• Breastfeeding: Metformin + Teneligliptin should not be used during breastfeeding as both drugs can be excreted in breast milk and may pose a risk to the nursing infant.

Drug Profile Summary

• Mechanism of Action: Metformin reduces hepatic glucose production, increases insulin sensitivity. Teneligliptin increases incretin hormone levels, leading to glucose-dependent insulin secretion.
• Side Effects: Nausea, vomiting, diarrhea, stomach upset, headache, hypoglycemia. Rare but serious: Lactic acidosis.
• Contraindications: Hypersensitivity, type 1 diabetes, severe renal impairment, diabetic ketoacidosis, heart failure.
• Drug Interactions: Alcohol, cationic drugs, some antibiotics and antifungals, other antidiabetic medications.
• Pregnancy & Breastfeeding: Not recommended during pregnancy or breastfeeding.
• Dosage: Starting dose: Metformin 500 mg + Teneligliptin 20 mg once daily; Max dose: Metformin 2000 mg + Teneligliptin 40 mg daily.
• Monitoring Parameters: Blood glucose levels, HbA1c, renal function (especially in the elderly), vitamin B12 levels (with long-term Metformin use).

Popular Combinations

• Often combined with other antidiabetic medications, such as sulfonylureas (e.g., glimepiride, gliclazide), thiazolidinediones (e.g., pioglitazone), or insulin, if needed for improved glycemic control.

Precautions

• General Precautions: Assess renal function, hepatic function, and cardiovascular status before initiating therapy.
• Specific Populations (As above)

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Metformin + Teneligliptin?

A: The starting dose is usually Metformin 500 mg + Teneligliptin 20 mg once daily, taken with food. The maximum dose is Metformin 2000 mg + Teneligliptin 40 mg daily, adjusted based on patient response and tolerability.

Q2: How does this combination work differently than Metformin or Teneligliptin alone?

A: The combination offers synergistic effects by targeting multiple pathways involved in glucose regulation. It provides better glycemic control than either drug alone in some patients.

Q3: What are the signs of lactic acidosis?

A: Symptoms include abdominal pain, muscle cramps, vomiting, severe fatigue, difficulty breathing, and general malaise. Lactic acidosis is a medical emergency.

Q4: Can I take this medication if I have kidney problems?

A: The dose needs to be adjusted or the combination avoided altogether depending on the severity of renal impairment. Discuss it with your physician to determine appropriate management.

Q5: Is this combination safe during pregnancy?

A: It’s generally not recommended. Insulin is often the preferred treatment for managing blood sugar during pregnancy. Consult with an obstetrician for guidance.

Q6: Can I drink alcohol while taking this medicine?

A: Alcohol should be avoided or limited as it can increase the risk of lactic acidosis and hypoglycemia.

Q7: Are there any dietary restrictions while on this medication?

A: A healthy diet is crucial for managing diabetes. This medication is taken with food to minimize gastrointestinal side effects. Consult a dietitian or nutritionist to create a personalized meal plan.

Q8: What should I do if I miss a dose?

A: Take the missed dose as soon as you remember unless it’s close to the time for the next dose. Do not double the dose to catch up.

Q9: What are the long-term effects I should be aware of?

A: Metformin can potentially decrease Vitamin B12 absorption over time, so regular monitoring of B12 levels may be advised.

Q10: Can this medicine be used with other diabetes medications?

A: Yes, Metformin + Teneligliptin can be used with other antidiabetic drugs, such as sulfonylureas or insulin, depending on individual needs and treatment goals, however there is an increased risk of hypoglycemia. This should be done under close medical supervision.