Glimepiride-Pioglitazone

Glimepiride-Pioglitazone is a combination medication used for the treatment of type 2 diabetes mellitus in patients treated with a combination of pioglitazone and a sulfonylurea, or patients not adequately controlled on a sulfonylurea alone, or who have initially responded to pioglitazone and require additional glycemic control management of diabetes mellitus as an adjunct to diet and exercise.

• Glimepiride-Pioglitazone is available under the following different brand names: Duetact.

Common side effects of Glimepiride-Pioglitazone include:

• symptoms associated with a cold (sneezing, stuffy nose, cough, sore throat)
• weight gain
• mild nausea
• diarrhea
• headache
• dizziness
• blurred vision
• tooth problems

Serious side effects of Glimepiride-Pioglitazone include:

• pink or red urine, painful or difficult urination, new or worsening urge to urinate
• changes in the vision
• sudden unusual pain in the hand, arm, or foot
• liver problems--upper stomach pain, vomiting, tiredness, loss of appetite, dark urine, jaundice (yellowing of the skin or eyes)
• symptoms of heart failure--shortness of breath (even while lying down), swelling in the legs or feet, rapid weight gain

Rare side effects of Glimepiride-Pioglitazone include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 30 mg/2 mg
• 30 mg/4 mg

Type 2 diabetes mellitus

Adult dosage

• 30 mg/2 mg, OR 30 mg/4 mg orally once a day; not to exceed 45 mg/8 mg

Geriatric dosage

• 1 mg/day glimepiride (as monotherapy) orally prior to initiating Glimepiride-Pioglitazone; titrate conservatively to avoid hypoglycemia

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Glimepiride-Pioglitazone has severe interactions with no other drugs
• Glimepiride-Pioglitazone has serious interactions with the following drugs:
  • aminolevulinic acid oral
  • aminolevulinic acid topical
  • baricitinib
  • eluxadoline
  • ethanol
  • gemfibrozil
  • ivosidenib
  • lumacaftor/ivacaftor
  • methyl aminolevulinate
  • pacritinib
• Glimepiride-Pioglitazone has moderate interactions with at least 213 other drugs
• Glimepiride-Pioglitazone has minor interactions with at least 147 other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Hypersensitivity
• Diabetic ketoacidosis with or without coma
• Active liver disease, increased serum transaminase levels
• Not recommended in heart failure NYHA III-IV patients

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Glimepiride-Pioglitazone?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Glimepiride-Pioglitazone?”

Cautions

• Increased risk of cardiovascular mortality
• Edema; thiazolidinediones, which are peroxisome proliferator-activated receptor (PPAR) gamma agonists, can cause dose-related fluid retention, particularly when used in combination with insulin
• Hemolytic anemia may occur with glucose 6-phosphate dehydrogenase (G6PD) deficiency when treated with sulfonylurea agents
• Fluid retention may occur and can exacerbate or lead to congestive heart failure; combination use with insulin and use in congestive heart failure NYHA Class I and II may increase risk; monitor patients for signs and symptoms
• Hypoglycemia may be severe. when insulin or an insulin secretagogue is used with pioglitazone, a lower insulin dose or insulin secretagogue dose may be needed to reduce the risk of hypoglycemia
• Postmarketing reports for glimepiride include anaphylaxis, angioedema, and Stevens-Johnson syndrome; promptly discontinue glimepiride, assess for other causes, institute appropriate monitoring and treatment, and initiate alternative treatment for diabetes
• Postmarketing reports of hepatic failure, sometimes fatal; causality cannot be excluded; if liver injury detected, promptly interrupt therapy and assess the patient for probable cause, then treat cause if possible, to resolution or stabilization; do not restart therapy if liver injury confirmed and no alternate etiology can be found
• Dose-related edema may occur
• Increased incidence of bone fracture reported
• Macular edema reported; recommend regular eye exams in all patients with diabetes according to current standards of care with prompt evaluation for acute visual changes
• No clinical studies establishing conclusive evidence of macrovascular risk reduction with Glimepiride-Pioglitazone or any other antidiabetic drug exist
• Increase in weight gain possibly related to pioglitazone effects on fluid retention and fat accumulation
• Cancer risk
  • Bladder cancer
  • Pioglitazone may be linked to an increased risk of bladder cancer
  • Do not prescribe for patients with active bladder cancer
  • Consider benefit: risk ratio before prescribing in patients with a history of bladder cancer
  • Instruct patients to contact their physician if signs of bladder cancer are observed after initiating therapy (eg, blood or red-colored urine, new or worsening urinary urgency, pain on urination)
• Prostate cancer
  • 7/22/2015: Compared with nonuse, pioglitazone use was associated with increased risk for prostate cancer (453.3 vs. 449.3 per 100,000 person-years) [JAMA 2015 July 21;314(3):265-277]
• Pancreatic cancer
  • 7/22/2015: Compared with nonuse, pioglitazone use was associated with increased risk for pancreatic cancer (81.1 vs. 48.4 per 100,000 person-years) [JAMA 2015 July 21;314(3):265-277]
• See also individual monographs
  • Pioglitazone
  • Glimepiride

Pregnancy and Lactation

• Limited data in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage; there are clinical considerations related to fetal and neonatal adverse reactions and drug discontinuation if glimepiride is used during pregnancy; there are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy
• Poorly controlled diabetes in pregnancy increases maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and stillbirth Not for treatment of type 1 diabetes or diabetic ketoacidosis, and delivery complications; poorly controlled diabetes increases fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity
• Neonates of women with gestational diabetes, who are treated with sulfonylureas during pregnancy, may be at increased risk for neonatal intensive care unit admission, and may develop respiratory distress, hypoglycemia, birth injury, and be large for gestational age; prolonged severe hypoglycemia, lasting 4-10 days, reported in neonates born to mothers receiving a sulfonylurea at time of delivery and has been reported with use of agents with a prolonged half-life; observe newborns for symptoms of hypoglycemia and respiratory distress and manage accordingly
• Due to reports of prolonged severe hypoglycemia in neonates born to mothers receiving a sulfonylurea at the time of delivery, therapy should be discontinued at least two weeks before the expected delivery
• Lactation
  • There is no information regarding the presence of pioglitazone or glimepiride in human milk, its effects on breastfed infants, or milk production; pioglitazone and glimepiride are present in rat milk; however, due to species-specific differences in lactation physiology, animal data may not reliably predict drug levels in human milk
  • The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on the breastfed infant from therapy or underlying maternal condition