Glipizide and Metformin

Glipizide and metformin hydrochloride tablets, USP are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Glipizide and metformin hydrochloride tablet combines glipizide and metformin hydrochloride, 2 antihyperglycemic agents with complementary mechanisms of action, to improve glycemic control in patients with type 2 diabetes. Glipizide appears to lower blood glucose acutely 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. The mechanism by which glipizide lowers blood glucose during long-term administration has not been clearly established. In man, stimulation of insulin secretion by glipizide in response to a meal is undoubtedly of major importance.

General Considerations: Dosage of glipizide and metformin hydrochloride tablets must be individualized on the basis of both effectiveness and tolerance while not exceeding the maximum recommended daily dose of 20 mg glipizide/2,000 mg metformin. Glipizide and metformin hydrochloride tablets should be given with meals and should be initiated at a low dose, with gradual dose escalation as described below, in order to avoid hypoglycemia (largely due to glipizide), reduce GI side effects (largely due to metformin), and permit determination of the minimum effective dose for adequate control of blood glucose for the individual patient. With initial treatment and during dose titration, appropriate blood glucose monitoring should be used to determine the therapeutic response to glipizide and metformin hydrochloride tablets and to identify the minimum effective dose for the patient.

Glipizide and metformin hydrochloride tablets are contraindicated in patients with: Severe renal impairment (eGFR below 30 mlL/min/1.73 m 2 ). Known hypersensitivity to glipizide or metformin hydrochloride. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Diabetic ketoacidosis should be treated with insulin. WARNINGS SPECIAL WARNING ON INCREASED RISK OF CARDIOVASCULAR MORTALITY The administration of oral hypoglycemic drugs has been reported to be associated with increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin.

LACTIC ACIDOSIS Post-marketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain.

Glipizide and Metformin Hydrochloride Tablets: In a double-blind 24 week clinical trial involving glipizide and metformin hydrochloride tablets as initial therapy, a total of 172 patients received glipizide and metformin hydrochloride tablets, 2.5 mg/250 mg, 173 received glipizide and metformin hydrochloride tablets, 2.5 mg/500 mg, 170 received glipizide, and 177 received metformin. The most common clinical adverse events in these treatment groups are listed in Table 4. Table 4 Clinical Adverse Events >5% in any Treatment Group, by Primary Term, in Initial Therapy Study Adverse Event Number (%) of Patients Glipizide Tablets 5 mg N=170 Metformin Tablets 500 mg N=177 Glipizide and Metformin Hydrochloride Tablets 2.5 mg/250 mg N=172 Glipizide and Metformin Hydrochloride Tablets 2.5 mg/500 mg N=173 Upper respiratory infection 12 15 17 14. Diarrhea 8 15 4 9. Dizziness 9 2 3 9.