BRAND NAMES
 MECHANISM OF ACTION
Repaglinide is a nonsulfonylurea secretagogue. It lowers blood glucose levels by stimulating the release of insulin from the pancreas. It achieves this by closing ATP-dependent potassium channels in the ß-cell membrane by binding at characterizable sites. This potassium channel blockade depolarizes the ß-cell, which leads to an opening of calcium channels. The resulting increased calcium influx induces insulin secretion. The ion channel mechanism is highly tissue selective with low affinity for heart and skeletal muscle.
In contrast to sulfonylureas, Repaglinide activity is glucose-dependent and diminishes at low glucose concentrations.
Repaglinide has been shown to be roughly as effective as the sulfonylureas at reducing HbA1c levels, causing a decrease of 1.5% to 2%.
Compared with sulfonylureas, Repaglinide:
- Has a shorter half-life and a rapid onset of action, making it an ideal agent for controlling postprandial hyperglycaemia
- Is less-like to induce hypoglycemia
- Can mimic better the physiological insulin secretion
Repaglinide is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Repaglinide doses are usually taken within 15 minutes of the meal but time may vary from immediately preceding the meal to as long as 30 minutes before the meal. Patients who skip a meal (or add an extra meal) should be instructed to skip (or add) a dose for that meal.
- Starting Dose: For patients not previously treated or whose HbA1c is < 8%, the starting dose should be 0.5 mg with each meal. For patients previously treated with blood glucose-lowering drugs and whose HbA1c is ≥ 8%, the initial dose is 1 or 2 mg with each meal preprandially
- Diabetic ketoacidosis (This condition should be treated with insulin)
- Type 1 diabetes
- Co-administration of gemfibrozil. (Gemfibrozil substantially increases repaglinide exposure)
- Known hypersensitivity to the drug or its inactive ingredients.
- Repaglinide is metabolized by CYP2C8 and CYP3A4. Consequently, repaglinide metabolism may be altered by drugs which influence these cytochrome P450 enzyme systems via induction and inhibition:
- CYP3A4 inhibitors like ketoconazole, itraconazole, nefazodone and macrolide antibiotics (e.g. erythromycin, clarithromycin), increase the systemic exposure to Repaglinide
- CYP2C8 inhibitors include agents (e.g. trimethoprim, gemfibrozil and montelukast), increase the systemic exposure to Repaglinide
- CYP3A4 and/or CYP2C8 inducers (e.g. rifampin, barbiturates, and carbamezapine) decrease the systemic exposure to Repaglinide
 PREGNANCY AND LACTATION
- Pregnancy Category C (US). Safety in pregnant women has not been established. Repaglinide should be used during pregnancy only if it is clearly needed. Because recent information suggests that abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital abnormalities, many experts recommend that insulin be used during pregnancy to maintain blood glucose levels as close to normal as possible.
- Nursing mothers: it is not known whether repaglinide is excreted in human milk. A decision should be made as to whether discontinue Repaglinide, or to discontinue nursing. If Repaglinide is discontinued and if diet alone is inadequate for controlling blood glucose, insulin therapy should be considered.
 SIDE EFFECTS
 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)|