Glipizide + Metformin Hydrochloride

Indications

Glipizide & Metformin is indicated as initial therapy, as an adjunct to diet and exercise, to improve glycemic control in patients with type 2 diabetes whose hyperglycemia cannot be satisfactorily managed with diet and exercise alone and as second-line therapy when diet, exercise, and initial treatment with a Sulfonylurea or Metformin do not result in adequate glycemic control in patients with type 2 diabetes

Pharmacology

Metformin is a biguanide antihyperglycemic agent, which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Its pharmacological mechanisms of action are different from other classes of oral antihyperglycemic agents. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. Unlike sulfonylurea, metformin does not produce hypoglycemia in either patient with type 2 diabetes or normal subjects and does not cause hyperinsulinemia.

Glipizide is a sulfonylurea which appears to lower blood glucose by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. Extrapancreatic effects may play a part in the mechanism of action of oral sulfonylurea hypoglycemic drugs.

Dosage & Administration

Glipizide & Metformin should be given once or twice daily with meals and should be initiated at a low dose, with gradual dose escalation.

Glipizide & Metformin as Initial Therapy: The recommended starting dose is 250 mg/2.5 mg once a day with meal.

Glipizide & Metformin as Second-Line Therapy: The recommended starting dose is 500 mg/2.5 mg or 500 mg/5 mg twice daily with the morning and evening meals. The maximum recommended daily dose is 2000 mg Metformin/20 mg Glipizide.

Interaction

Cimetidine reduces the renal clearance of Metformin. Alcohol potentiates the antihyperglycemic & hyperlactataemic effect of Metformin. It may enhance the effects of anti-coagulants. Such patients receiving the two drugs may need adjustment of the anti-coagulant dosage. Nifedipine appears to enhance the absorption of Metformin but Metformin has minimal effects on Nifedipine. The hypoglycemic action of sulfonylureas may be potentiated by certain drugs including nonsteroidal anti-inflammatory agents, some azoles, and other drugs that are highly protein bound, salicylates, sulfonamides, chloramphenicol, probenecid, coumarins, monoamine oxidase inhibitors, and beta adrenergic blocking agents.

Contraindications

Hypersensitivity to the drug, renal impairment, diabetic coma and ketoacidosis, chronic renal diseases, congestive heart failure, trauma, dehydration, alcohol dependence, pregnancy, breast-feeding etc.

Side Effects

The most common side effects of Glipizide & Metformin are hypoglycemia,
diarrhea, nausea/vomiting, abdominal pain, headache, musculoskeletal pain etc.

Pregnancy & Lactation

Contraindicated during Pregnancy & Lactation

Precautions & Warnings

Metformin is known to be substantially excreted by the kidney, and the risk of Metformin accumulation and lactic acidosis is increased with the degree of impairment of renal function. Thus, patients with serum creatinine levels above the upper limit of normal should not receive Metformin. In patients with advanced age, Metformin should be carefully titrated to establish minimum dose for adequate glycemic control, because aging is associated with reduced renal function. Metformin therapy should be temporarily suspended for any surgical procedure and should not be restarted until the patient’s oral intake has resumed and renal function has been evaluated as normal. During concomitant therapy with sulfonylurea, blood glucose should be monitored. Metformin & insulin therapy should be carried out in hospital until the correct ratio of the two drugs has been established. The metabolism and excretion of Glipizide may be slowed in patients with impaired renal and/or hepatic function. If hypoglycemia should occur in such patients, it may be prolonged and appropriate management should be instituted.

Therapeutic Class

Combination Oral hypoglycemic preparations

Storage Conditions

Store below 25ºC in a cool and dry place.