Alogliptin/Metformin

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Contents

[edit] BRAND NAMES

[edit] STRUCTURE

[edit] MECHANISM OF ACTION

This is a combination of two antidiabetic medications with complementary and distinct mechanisms of action:

  • 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.


  • Metformin is an antidiabetic medication, it acts primarily by decreasing endogenous hepatic glucose production (gluconeogenesis). Metformin also decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
    Metformin lowers both basal and postprandial plasma glucose and unlike sulfonylureas, it is not associated with substantial risk for hypoglycemia.
    Metformin as monotherapy remains the only agent associated with weight loss in patients with obesity with non-insulin-dependent diabetes mellitus (NIDDM). The mechanism may be attributed to decreased food intake [1].
    Metformin is currently considered to be one of the first-choice drugs for type 2 diabetes mellitus, in particular, in overweight and obese people.
    Metformin also has neutral to positive effects on LDL cholesterol and triglyceride levels.

[edit] INDICATIONS

Alogliptin/Metformin combination 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 metformin is appropriate.

Alogliptin/Metformin combination should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.

[edit] DOSAGE

Starting dosage should be individualized, based on the patient’s current regimen, effectiveness and tolerability. The maximum recommended daily dose is 25 mg alogliptin and 2000 mg of metformin.

Tablets should be taken twice daily with food, or just after food, to reduce gastrointestinal symptoms associated with metformin.

[edit] DOSAGE FORMS AND STRENGTHS

[edit] CONTRAINDICATIONS

  • Hypersensitivity to Alogliptin or Metformin
  • Renal impairment (e.g., serum creatinine levels ≥1.5 mg/dL for men, ≥1.4 mg/dL for women or abnormal creatinine clearance). Risk of metformin accumulation and lactic acidosis increases with the degree of impairment.
  • Metabolic acidosis including diabetic ketoacidosis with or without coma. (Diabetic ketoacidosis should be treated with insulin)
  • Intravascular administration of iodinated contrast agents (it can lead to acute alteration of renal function and have been associated with lactic acidosis in patients receiving metformin)

[edit] WARNINGS AND PRECAUTIONS

  • Lactic acidosis is a very rare (0.03 cases/1000 patient/year), but serious, metabolic complication that can occur due to metformin accumulation (primarily reported in diabetic patients with significant renal failure). The risk increases also with conditions such as sepsis, dehydration, excess alcohol intake, hepatic impairment, and acute congestive heart failure. Symptoms include respiratory distress, abdominal pain , malaise, myalgias, increasing somnolence and hypothermia. If metabolic acidosis is suspected, treatment with the medicinal product should be discontinued and the patient hospitalised immediately.
  • There have been postmarketing reports of acute pancreatitis in patients taking alogliptin. Patients should be observed for signs and symptoms of pancreatitis
  • Hypersensitivity reactions: There have been postmarketing reports of serious hypersensitivity reactions in patients treated with alogliptin. These reactions include anaphylaxis, angioedema, and severe cutaneous adverse reactions including Stevens-Johnson syndrome. If a serious hypersensitivity reaction is suspected, discontinue the drug. Use also with caution in patients with a history of angioedema to another DPP-4 inhibitor
  • 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 in patients taking alogliptin)
  • Vitamin B12 deficiency: Metformin may lower vitamin B12 levels. Monitor hematologic parameters annually
  • Avoid excessive alcohol intake

[edit] INTERACTIONS

  • A lower dose of Insulin secretagogue, (e.g., sulfonylurea) or insulin dosage when used in combination with Alogliptin/Metformin may be required to minimize the risk of hypoglycemia

[edit] PREGNANCY AND LACTATION

  • Pregnancy Category B (US). Alogliptin/Metformin combination like other antidiabetic medications, should be used during pregnancy only if clearly needed
  • It is not known whether alogliptin and/or metformin are secreted in human milk. Caution should be exercised when Alogliptin/Metformin combination is administered to a nursing woman

[edit] SIDE EFFECTS

Common adverse reactions reported in ≥4% of patients treated with coadministration of alogliptin with metformin were: upper respiratory tract infection, nasopharyngitis, diarrhea, hypertension, headache, back pain and urinary tract infection.

Serious hypersensitivity reactions in patients treated with alogliptin. These reactions include anaphylaxis, angioedema, and severe cutaneous adverse reactions including Stevens-Johnson syndrome.

[edit] RELATED LINKS

[edit] BIBLIOGRAPHY

Takeda PRESCRIBING INFORMATION

[edit] REFERENCES

  1. http://www.ncbi.nlm.nih.gov/pubmed/9526970
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)
Biguanides Metformin (Glucophage)
Thiazolidinediones Pioglitazone (Actos)
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)
Combination therapy
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)