Pioglitazone and glimepiride (Duetact, Piozer-G) is a combination of two anti-diabetic drugs: Pioglitazone and Glimipiride. Pioglitazone is a thiozolidenedione while glimipiride is a sulfonylurea.

Indications of pioglitazone and glimepiride:

• Type II diabetes mellitus:

  • It is used to address type 2 diabetes mellitus in patients who have either received insufficient control from either medication alone or who have already had treatment with thiazolidinedione and sulfonylurea.

Pioglitazone and glimepiride (Duetact, Piozer-G) dose in adults:

The treatment dose of type 2 Diabetes mellitus:

Based on current pioglitazone and/or sulfonylurea dosage, the initial dose should be determined.

• Patients inadequately controlled on glimepiride alone:

  • Pioglitazone 30 mg/glimepiride 2 mg or 30 mg/glimepiride 4 mg orally once day is the recommended starting dose.

• Patients inadequately controlled on pioglitazone alone:

  • Pioglitazone 30 mg/glimepiride 2 mg orally once day is the recommended starting dose.

• Patients switching from pioglitazone plus a sulfonylurea combination medication or those who are presently receiving sulfonylurea monotherapy (other than glimepiride) (other than glimepiride):

  • Pioglitazone 30 mg/glimepiride 2 mg once day, starting dose. Due to overlapping hypoglycemia effects, patients who are switching from other sulfonylureas with longer half-lives (such as chlorpropamide) to glimepiride should be monitored closely for 1–2 weeks.

• Patients with systolic dysfunction (eg, NYHA Class I and II):

  • Do not start treatment until the patient has safely increased their pioglitazone dosage to 30 mg. Pioglitazone 30 mg/glimepiride 2 mg orally once day is the recommended starting dose.

• Dosage adjustment:

  • Depending on effectiveness and tolerance, the dosage may be adjusted up to a maximum of pioglitazone 45 mg/glimepiride 8 mg per mouth once daily.
  • It is crucial to watch for symptoms of worsening heart failure and make careful dosage adjustments.

• Dosage adjustment for hypoglycemia with combination therapy:

  • Reduce the dose of an insulin secretagogue while using one.
  • Reduce the insulin dose by 10 to 25% when using it.

Use in Children:

It is not recommended in children

Pregnancy & lactation

• You can contact individual agents.

Use of pioglitazone or glimepiride during breastfeeding

• If pioglitazone or glimepiride are secreted in breast milk, it is unknown.
• According to the manufacturer, whether or not to continue nursing depends on the risks and advantages for the baby as well as the mother.
  Identify specific agents.

Dose adjustment in renal disease:

There are no specific dosage adjustments provided in the manufacturer’s labeling. Dose adjustment should be done conservatively.

Dose adjustment in liver disease:

• Hepatic impairment before initiation

  • The manufacturer's labeling does not include any dosage adjustments.

• Therapy for hepatic impairment

  • In cases of liver injury, therapy should be stopped. Serum liver tests should also be performed to determine if there are other causes.
    • Do not restart therapy if ALT is greater than 3x the upper limit of normal without any known cause.
    • If ALT is elevated (but less than 3x ULN) without any known cause, or total bilirubin elevation (but less than 2x ULN),: You may need to reinitiate caution.

Common Side Effects of Pioglitazone and glimepiride (Duetact, Piozer-G):

• Cardiovascular:

  • Peripheral Edema

• Endocrine & Metabolic:

  • Hypoglycemia
  • Weight Gain

• Respiratory:

  • Upper Respiratory Tract Infection

Rare Side Effects Of Pioglitazone and glimepiride (Duetact, Piozer-G):

• Central Nervous System:

  • Headache

• Gastrointestinal:

  • Diarrhea
  • Nausea

• Genitourinary:

  • Urinary Tract Infection

• Hematologic & Oncologic:

  • Anemia

• Neuromuscular & Skeletal:

  • Limb Pain

Contraindications to Pioglitazone and glimepiride (Duetact, Piozer-G):

• Hypersensitivity to glimepiride, pioglitazone, or any component of the formulation
• Class III or IV heart failure
• history of an allergic reaction to sulfonamide derivatives

Note:

Although the FDA-approved product labelling warns that this medication should not be taken with other groups of drugs that contain sulfonamides, the scientific validity of this claim has been questioned.

Warnings and Precautions

• Bladder cancer

  • Patients with bladder carcinoma should not be given pioglitazone.
  • Manufacturer recommends that patients with active bladder cancer avoid the product and weigh the risks against the benefits before initiating treatment in patients who have had bladder cancer in the past.

• Cardiovascular mortality

  • The product labeling clearly states that oral antidiabetics, taken alone, can increase the risk of developing cardiovascular events.
  • Alternative medications should be prescribed to patients with atherosclerotic cardiovascular disease.

• Edema

  • Pioglitazone can cause new-onset or worsening of existing edema.
  • Keep an eye out for symptoms and signs of heart failure.

• Fractures

  • Pioglitazone may increase fracture risk, particularly in the lower limbs and distal upper extremities.

• Heart Failure/cardiac Effects: [US Boxed Warn]

  • You should look out for signs and symptoms such as weight gain, rapid dyspnoea, and edema. Dose reductions or discontinuations should be made.
  • It should not be used by anyone who have heart disease or who are in NYHA classes III or IV.
  • The lowest dose should be administered to patients who have heart failure according to NYHA classes II or I.

• Hematologic effects

  • Pioglitazone may cause anemia from increased plasma volume.

• Hepatic effects

  • It could lead to life-threatening liver failure.
  • If you notice signs or symptoms of liver injury, it is important to stop treating.

• Hypersensitivity reactions

  • Hypersensitivity reactions can occur when oral antidiabetics are taken.
  • Supportive management should be initiated immediately and the drug must be stopped immediately.

• Hypoglycemia

  • All sulfonylurea medications can cause severe hypoglycemia.
  • Hypoglycemia can be caused by several factors, including old age, malnourishment and hepatic function, prolonged exercise, alcohol intake, and multi-drug treatment for diabetes.

• Macular edema

  • Macular edema can cause blurred vision and decreased visual acuity.
  • Regular ophthalmic exams should be performed.

• Allergy to sulfonamide ("sulfa")

  • FDA-approved product labels for medications that contain sulfonamide chemical groups include a wide contraindication for patients who have had an allergic reaction to sulfonamides in the past.
  • The possibility of cross-reactivity between antibiotic and non-antibiotic sulfonamides may not exist as a result of improved knowledge of allergic processes.
  • Additionally, this class of medications has a history of producing type IV T cell reactions such maculopapular eruptions.
  • If you experience severe reactions like Stevens Johnson syndrome or toxic epidermal necrolysis, you shouldn't take this class of medications.

• Weight loss

  • Pioglitazone causes fat deposition and fluid retention, which results in weight gain.

• Bariatric surgery

  • Absorption altered:
    • Immediate-release formulations should always be utilised to reduce any potential effects of bypassing the stomach or proximal bowel with gastric bypass or quicker gastric emptying and proximal bowel transit with Sleeve gastrectomy.
    • On the other hand, after a gastric bypass or sleeve gastrectomy, extended-release formulations may alter the release and absorption patterns (but no gastric-band).
  • Hypoglycemia
    • Anti-diabetics can cause hypoglycemia in the stomach.
    • These procedures may result in a partial or complete restoration of insulin secretion and sensitivity.
    • The recovery process for peripheral insulin sensitivity can take between 3-12 months.
  • Weight loss
    • Alternate agents should be utilised following gastric bypass, gastric banding, or sleeve gastrectomy. Weight gain may result from this.

• Glucose-6phosphate dehydrogenase(G6PD) deficiency

  • Patients with G6PD deficiencies are at greater risk for hemolytic anemia. Therefore, patients should receive a non-sulfonylurea.

• Hepatic impairment

  • Before and during treatment, it is important to monitor liver function.
  • If there are any indications or symptoms of liver damage, such as lethargy, anorexia, or jaundice, pioglitazone should not be administered.
  • Hypoglycemia is more common in patients with hepatic impairment who are also receiving glimepiride.
  • Therapy should be stopped if serum ALT exceeds 3 times the ULN. Patients at greater risk for liver injury are those with serum ALT above 3 times the ULN or serum total bilirubin below 2 times the ULN.

• Impairment of renal function:

  • Patients with impaired renal function may experience hypoglycemia.

• Stress-related disorders:

  • Withholding treatment and insulin should be used to manage stress from fever, trauma, infected, or surgery.

Pioglitazone and glimepiride: Drug Interaction

Monitoring parameters:

• Hemoglobin A 
• serum glucose.
• Liver function tests (before or during therapy)
• Ophthalmic exam
• Weight gain
• Heart failure symptoms
• Bladder cancer symptoms 

How to administer Pioglitazone and glimepiride (Duetact, Piozer-G)?

It should be taken orally daily with your first main meal of each day. Patients who do not have oral intake may be required to keep the dose.

Mechanism of action of Pioglitazone and glimepiride (Duetact, Piozer-G):

Pioglitazone

• For it to be active, it must have insulin. Thiazolidinedione improves insulin response in target cells, which results in lower blood glucose levels and decreased insulin secretion.

Glimepiride

• A sulfonylurea lowers liver glucose production while stimulating pancreatic beta cell release of insulin. This improves peripheral targets' sensitivity to insulin.

See individual agents: Pioglitazone, and Glimipiride  

International Brands of Pioglitazone and glimepiride:

• Duetact
• Actoril
• Actosryl
• Adride P
• Asenza Plus
• Diatag Plus
• Glitaglim
• Pioglit G
• Sonias
• Tandemact
• Tosirin
• Zanoglide
• Zoliget
• Zorep-1
• Zorep-2

Pioglitazone and Glimipiride Brands in Pakistan: