BRAND NAMES
 MECHANISM OF ACTION
This is a combination of two antidiabetic medications with complementary and distinct mechanisms of action:
- 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.
- Alogliptin: Incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released into the bloodstream from the small intestine in response to meals. These hormones cause insulin release from the pancreatic beta cells in a glucose-dependent manner but are inactivated by the DPP-4 enzyme within minutes. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, reducing hepatic glucose production. In patients with type 2 diabetes, concentrations of GLP-1 are reduced but the insulin response to GLP-1 is preserved. Alogliptin is a DPP-4 inhibitor that slows the inactivation of the incretin hormones, thereby increasing their bloodstream concentrations and reducing fasting and postprandial glucose concentrations in a glucose-dependent manner in patients with type 2 diabetes mellitus.
Alogliptin/Pioglitazone is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings when treatment with both alogliptin and pioglitazone is appropriate
The recommended starting dose for Alogliptin/Pioglitazone is:
- for patients inadequately controlled on diet and exercise is 25 mg/15 mg or 25 mg/30 mg,
- for patients inadequately controlled on metformin monotherapy is 25 mg/15 mg or 25 mg/30 mg,
- for patients on alogliptin who require additional glycemic control is 25 mg/15 mg or 25 mg/30 mg,
- for patients on pioglitazone who require additional glycemic control is 25 mg/15 mg, 25 mg/30 mg, or 25 mg/45 mg as appropriate based upon current therapy
- for patients switching from alogliptin coadministered with pioglitazone, Alogliptin/Pioglitazone may be initiated at the dose of alogliptin and pioglitazone based upon current therapy,
- for patients with congestive heart failure (NYHA Class I or II) is 25 mg/15 mg.
The dose can be titrated up to a maximum of 25 mg/45 mg once daily based on glycemic response as determined by hemoglobin A1c (A1C).
- Hypersensitivity to Pioglitazone or Alogliptin
- Cardiac failure (NYHA Class III or IV). Pioglitazone can cause fluid retention, which may exacerbate or precipitate heart failure.
- 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
- There have been postmarketing reports of acute pancreatitis in patients taking alogliptin. Patients should be observed for signs and symptoms of pancreatitis.
- Elderly: In light of age-related risks (especially bladder cancer, fractures and heart failure), the balance of benefits and risks should be considered carefully both before and during treatment in the elderly.
- 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.
- Hepatic Effects: Measure liver enzymes promptly in patients who report symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice. (Because of postmarketing reports of fatal and non-fatal hepatic failure)
- 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
- Weight should be closely monitored (weight gain can be due to fat accumulation, fluid retention or may be a symptom of cardiac failure)
- Ovulation: Therapy with pioglitazone, like other thiazolidinediones, may result in ovulation in some premenopausal anovulatory women. Adequate contraception in all premenopausal women is recommended.
- Fractures: Increased incidence in female patients.
- Gemfibrozil (an inhibitor of CYP2C8) increases Pioglitazone exposure approximately 3-fold, therefore, the maximum recommended dose of Alogliptin/Pioglitazone is 25 mg/15 mg
- A lower dose of Insulin secretagogue, (e.g., sulfonylurea) or insulin dosage when used in combination with Alogliptin/Pioglitazone may be required to minimize the risk of hypoglycemia
 PREGNANCY AND LACTATION
- Pregnancy Category C (US), Alogliptin/Pioglitazone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
- In nursing mothers a decision should be made to discontinue nursing or discontinue Alogliptin/Pioglitazone, taking into account the importance of the drug to the mother.
 SIDE EFFECTS
Possible side effects include: Nasopharyngitis, back pain and upper respiratory tract infections, Headache, Hypoglycemia
Serious adverse reactions: Congestive heart failure, Edema and Fractures (See Precautions)
Serious hypersensitivity reactions in patients treated with alogliptin. These reactions include anaphylaxis, angioedema, and severe cutaneous adverse reactions including Stevens-Johnson syndrome.
 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)|