BRAND NAMES
 MECHANISM OF ACTION
This is a combination of two antidiabetic medications with complementary and distinct mechanisms of action: Pioglitazone, a member of the thiazolidinedione class and Glimepiride, a member of the sulfonylureas class.
- Pioglitazone: Pioglitazone is a member of the thiazolidinedione class, it acts primarily by reducing insulin resistance in muscle and adipose tissue and by inhibiting hepatic gluconeogenesis. Pioglitazone is an agonist for peroxisome proliferator-activated receptor-gamma (PPARγ). PPAR receptors are found in tissues important for insulin action such as adipose tissue, skeletal muscle, and liver. Activation of PPARγ nuclear receptors modulates the transcription of a number of insulin responsive genes involved in the control of glucose and lipid metabolism.
- Glimepiride acts primarily by stimulating the release of insulin from functioning pancreatic beta cells.
Pioglitazone/Glimepiride is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are already treated with a thiazolidinedione and a sulfonylurea or who have inadequate glycemic control on a thiazolidinedione alone or a sulfonylurea alone
Dosage should be based on the patient's current regimen of pioglitazone and/or sulfonylurea, effectiveness and tolerability.
- Hypersensitivity to Pioglitazone or Glimepiride
- Cardiac failure (NYHA Class III or IV). Pioglitazone can cause fluid retention, which may exacerbate or precipitate heart failure.
- Diabetic ketoacidosis, with or without coma.
- Congestive Heart Failure: Pioglitazone, like other thiazolidinediones, can cause dose-related fluid retention when used alone or in combination with other antidiabetic medications, especially with insulin. Fluid retention may lead to or exacerbate congestive heart failure. Patients should be observed for signs and symptoms of congestive heart failure. If congestive heart failure develops, it should be managed according to current standards of care and discontinuation or dose reduction of pioglitazone must be considered
- Weight should be closely monitored (weight gain can be due to fat accumulation, fluid retention or may be a symptom of cardiac failure)
- Bladder Cancer: Available epidemiological data suggest a small increased risk of bladder cancer in diabetic patients treated with pioglitazone in particular in patients treated for the longest durations and with the highest cumulative doses. A possible risk after short term treatment cannot be excluded. For this reason both France and Germany have withdrawn pioglitazone products from the market.
- Ovulation: Therapy with pioglitazone, like other thiazolidinediones, may result in ovulation in some premenopausal anovulatory women. Adequate contraception in all premenopausal women is recommended.
- Pioglitazone/Glimepiride may cause decreases in hemoglobin and hematocrit
- It is recommended that liver enzymes be monitored periodically
- Macular edema has been reported in postmarketing experience in diabetic patients who were taking pioglitazone or another thiazolidinedione, therefore patients should have regular eye exams by an ophthalmologist
- Fractures: Increased incidence in female patients.
- Gemfibrozil (an inhibitor of CYP2C8) increases Pioglitazone exposure approximately 3-fold
 PREGNANCY AND LACTATION
- Pregnancy Category C (US), Pioglitazone/Glimepiride should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
- Pioglitazone/Glimepiride should not be administered to a woman breastfeeding
 SIDE EFFECTS
Common side effects: cold-like symptoms (upper respiratory infection), headache, urinary tract infection, diarrhea, nausea, and arm or leg pain. Other more serious side effects are listed under Precautions paragraph.
 RELATED LINKS
|Diabetes (Antidiabetic drugs)|
|Insulin Secretagogues (drugs that increase insulin release from pancreas)||Sulfonylureas||Chlorpropamide (Diabinese) • Glibenclamide or Glyburide (Diabeta, Micronase, Glynase, Daonil, Euglycon) • Gliclazide (Diamicron) • Glimepiride (Amaryl, Solosa) • Glipizide (Glucotrol, Minidiab, Glibenese) • Gliquidone (Glurenorm)|
|Meglitinides||Repaglinide (Prandin, Novonorm) • Nateglinide (Starlix)|
|Dipeptidyl peptidase-4 inhibitors||Linagliptin (Trajenta) • Saxagliptin (Onglyza) • Sitagliptin (Januvia) • Vildagliptin (Galvus)|
|Incretin mimetics (GLP-1 agonists and analogs)||Exenatide (Byetta) • Liraglutide (Victoza) • Lixisenatide (Lyxumia) • Dulaglutide (Trulicity)|
|Insulin Sensitizers (drugs that decrease insulin resistance)|
|Drugs that retard the digestion and absorption of carbohydrates in the small intestine|
|Alpha-glucosidase inhibitors||Acarbose (Glucobay, Precose)|
|Drugs that reduce glucose absorption in the kidney and increase glucose excretion in the urine|
|Sodium glucose cotransporter 2 (SGLT2) inhibitors||Canagliflozin (Invokana) • Dapagliflozin (Farxiga) • Empagliflozin (Jardiance, Glyxambi, Synjardi)|
|Insulin and insulin analogs|
|Intermediate acting insulins||Insulin lispro protamine (Humalog BASAL) • Isophane human insulin : Human insulin protamine (NPH) (Humulin I, Protaphane)|
|Long-acting insulins||Insulin detemir (Levemir) • Insulin glargine (Lantus)|
|Fast-acting insulins||Regular insulin : Insulin (Human recombinant) (Actrapid, Humulin R)|
|Ultra-rapid-acting insulins||Insulin aspart (Novorapid) • Insulin glulisine (Apidra) • Insulin lispro (Humalog) • Insulin human (Inhalation Powder) (Afrezza)|
|Premixed insulin (ultra-rapid-acting + intermediate acting||Insulin aspart / Insulin aspart protamine (Novomix) • Insulin lispro / Insulin lispro protamine (Humalog Mix)|
|Inhaled Insulin||Insulin human (Inhalation Powder) (Afrezza)|
|Sulfonylurea + Metformin||Glibenclamide / Metformin (Bieuglicon M, Diaglimet, Glibomet, Gliconorm, Glicorest, Suguan M)|
|Thiazolidinedione + Metformin||Pioglitazone / Metformin (Competact, Glubrava)|
|Thiazolidinedione + Sulfonylurea||Pioglitazone / Glimepiride (Tandemact)|
|Dipeptidyl peptidase-4 inhibitors + Metformin||Linagliptin / Metformin (Jentadueto) • Sitagliptin / Metformin (Efficib, Janumet, Velmetia) • Vildagliptin / Metformin (Eucreas)|