Usage
- Pioglitazone + Teneligliptin is prescribed for the management of type 2 diabetes mellitus in adults, specifically when diet and exercise alone or treatment with either Pioglitazone or Teneligliptin alone does not provide adequate glycemic control. It may also be used as a second-line treatment for type 2 diabetes when lifestyle modifications and initial single antidiabetic medications haven’t achieved sufficient glycemic control.
- Pharmacological Classification: Antidiabetic combination therapy. Specifically, it combines a thiazolidinedione (Pioglitazone) and a dipeptidyl peptidase-4 (DPP-4) inhibitor (Teneligliptin).
- Mechanism of Action: Pioglitazone increases insulin sensitivity in peripheral tissues (muscle, adipose tissue) by activating PPAR-γ receptors. Teneligliptin inhibits DPP-4 enzyme activity, increasing the levels of incretin hormones (GLP-1 and GIP). This leads to enhanced glucose-dependent insulin secretion and suppressed glucagon release.
Alternate Names
- This combination therapy doesn’t have an international nonproprietary name (INN). It is commonly referred to by the names of its constituents, Pioglitazone and Teneligliptin.
- Brand Names: Teneligold Pio, other brand names may exist regionally.
How It Works
- Pharmacodynamics: Pioglitazone improves insulin sensitivity in peripheral tissues, reducing insulin resistance. Teneligliptin enhances glucose-dependent insulin secretion and suppresses glucagon release, improving postprandial and fasting glucose levels.
- Pharmacokinetics:
- Pioglitazone: Absorbed well orally, extensively metabolized in the liver (primarily by CYP2C8 and CYP3A4), has a half-life of 5-6 hours (parent drug) and 16-23 hours (active metabolites), eliminated primarily through biliary/fecal excretion.
- Teneligliptin: Well absorbed orally, metabolized by FMO3, FMO1, CYP3A4 and CYP2D6, has a longer half-life of approximately 24 hours, primarily excreted in urine (about 20% as unchanged drug).
- Mode of Action: Pioglitazone activates PPAR-γ, a nuclear receptor that regulates gene expression related to glucose and lipid metabolism. Teneligliptin inhibits DPP-4, preventing the degradation of incretin hormones, thus enhancing their effects on insulin secretion and glucagon suppression.
- Receptor Binding/Enzyme Inhibition: Pioglitazone binds to and activates PPAR-γ receptors. Teneligliptin inhibits the enzyme DPP-4.
- Elimination Pathways: Pioglitazone is primarily eliminated through hepatic metabolism and biliary/fecal excretion. Teneligliptin is primarily eliminated through hepatic metabolism and renal excretion.
Dosage
Standard Dosage
Adults:
- One tablet containing 20 mg Teneligliptin and either 15 mg or 30 mg of Pioglitazone, taken orally once daily. This can be taken with or without food.
- Dosage may be adjusted based on individual patient response and tolerability.
Children:
- This medication is not recommended for children under 18 years of age. Safety and efficacy have not been established in pediatric patients.
Special Cases:
- Elderly Patients: No specific dosage adjustment is typically required unless there is significant renal or hepatic impairment. Close monitoring is advisable.
- Patients with Renal Impairment: Teneligliptin’s dosage does not require adjustment in patients with renal impairment. Pioglitazone requires caution and potential dosage adjustment in moderate to severe renal impairment.
- Patients with Hepatic Dysfunction: Pioglitazone is not recommended in patients with moderate to severe hepatic impairment. Teneligliptin may require dosage adjustments in severe hepatic impairment.
- Patients with Comorbid Conditions: Exercise caution in patients with heart failure, bladder cancer history, and other conditions. Individualized assessment and dosage adjustments may be needed.
Clinical Use Cases
- Not typically used in these acute care settings. Standard diabetes management applies in such cases.
Dosage Adjustments
- Dosage modifications may be required based on renal or hepatic function, concomitant medications, and individual patient response.
Side Effects
Common Side Effects
- Upper respiratory tract infections
- Headache
- Hypoglycemia (especially with concomitant insulin or sulfonylureas)
- Peripheral edema (Pioglitazone)
- Weight gain (Pioglitazone)
- Gastrointestinal disturbances (nausea, diarrhea)
Rare but Serious Side Effects
- Hepatic dysfunction (Pioglitazone)
- Bladder cancer (Pioglitazone)
- Heart failure (Pioglitazone)
- Severe hypoglycemia
- Hypersensitivity reactions
Long-Term Effects
- Increased risk of fractures (Pioglitazone)
- Potential for weight gain (Pioglitazone)
Adverse Drug Reactions (ADR)
- Angioedema
- Hepatitis
- Severe hypoglycemia requiring hospitalization
Contraindications
- Hypersensitivity to Pioglitazone or Teneligliptin
- Diabetic ketoacidosis
- Moderate to severe renal impairment (Pioglitazone)
- Active bladder cancer or history of bladder cancer (Pioglitazone)
- Heart failure NYHA class III or IV (Pioglitazone)
- Pregnancy (unless benefits clearly outweigh risks)
- Breastfeeding
Drug Interactions
- Insulin and sulfonylureas (increased risk of hypoglycemia)
- Gemfibrozil
- Rifampicin (reduces Pioglitazone levels)
- Ketoconazole (may increase Teneligliptin levels)
Pregnancy and Breastfeeding
- Not recommended during pregnancy unless clearly needed, potential risk to the fetus.
- Contraindicated during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Pioglitazone increases insulin sensitivity, Teneligliptin increases incretin hormone levels.
- Side Effects: Hypoglycemia, edema, weight gain, upper respiratory infections, headache, GI disturbances.
- Contraindications: Hypersensitivity, diabetic ketoacidosis, renal/hepatic impairment, bladder cancer, heart failure NYHA III/IV.
- Drug Interactions: Insulin, sulfonylureas, gemfibrozil, rifampicin, ketoconazole.
- Pregnancy & Breastfeeding: Not recommended during pregnancy, contraindicated in breastfeeding.
- Dosage: One tablet of Pioglitazone + Teneligliptin daily.
- Monitoring Parameters: HbA1c, fasting and postprandial blood glucose, liver function tests, renal function (especially for Pioglitazone).
Popular Combinations
- Metformin is sometimes used in combination with Pioglitazone and Teneligliptin in patients not adequately controlled with dual therapy.
Precautions
- Monitor liver function tests, renal function (especially for Pioglitazone), blood glucose levels regularly.
- Avoid alcohol (may increase risk of hypoglycemia and lactic acidosis with Metformin if used concomitantly).
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Pioglitazone + Teneligliptin?
A: One tablet containing 20mg of Teneligliptin and 15mg or 30mg of Pioglitazone, taken orally once daily.
Q2: How does this combination work in diabetes management?
A: Pioglitazone increases insulin sensitivity while Teneligliptin increases incretin levels, enhancing insulin secretion and suppressing glucagon.
Q3: What are the common side effects?
A: Hypoglycemia, upper respiratory infections, headache, peripheral edema, weight gain.
Q4: Are there any serious side effects to be aware of?
A: Yes, rare but serious side effects include hepatic dysfunction, bladder cancer (with Pioglitazone), and severe hypoglycemia.
Q5: Can this combination be used in pregnancy?
A: Generally, it’s not recommended during pregnancy unless clearly necessary due to potential fetal risks.
Q6: Is it safe to use while breastfeeding?
A: No, it is contraindicated during breastfeeding.
Q7: What are the major drug interactions?
A: Interactions can occur with insulin, sulfonylureas, gemfibrozil, rifampicin, and ketoconazole.
Q8: What are the contraindications for this drug?
A: Hypersensitivity, diabetic ketoacidosis, certain stages of heart failure, bladder cancer (current or history), and moderate to severe renal/hepatic impairment.
Q9: What monitoring parameters are important for patients on this combination?
A: Regular monitoring of HbA1c, fasting and postprandial glucose, liver function, and renal function (especially for Pioglitazone use) is essential.
