Adult: Glipizide 2.5 mg and metformin 250 mg tab Glipizide 2.5 mg and metformin 500 mg tab Glipizide 5 mg and metformin 500 mg tab
As an adjunct to diet and exercise: Dose is individualised based on effectiveness and tolerance. In patients with inadequate glycaemic control on diet and exercise alone: Initially, 2.5 mg/250 mg once daily. In patients with fasting plasma glucose (FPG) of 280-320 mg/dL, may give an initial dose of 2.5 mg/500 mg bid. May adjust dose every 2 weeks up to a Max of 10 mg/1,000 mg or 10 mg/2,000 mg daily in divided doses. In patients with inadequate glycaemic control on a sulfonylurea and/or metformin: Initially, 2.5 mg/500 mg or 5 mg/500 mg bid; initial dose must not exceed the daily dose of glipizide (or another sulfonylurea equivalent) and/or metformin already being taken. Titrate daily dose in increments of no more than 5 mg/500 mg. Max: 20 mg/2,000 mg daily.
Renal Impairment
Severe (eGFR <30 mL/min/1.73 m2): Contraindicated.
Administration
Should be taken with food.
Contraindications
Acute or chronic metabolic acidosis with or without coma (including diabetic ketoacidosis). Severe renal impairment (eGFR <30 mL/min/1.73 m2).
Special Precautions
Patient with G6PD deficiency, stable heart failure, stress-related state (e.g. fever, trauma, infection, surgery), adrenal or pituitary insufficiency; risk factors for hypoglycaemia (e.g. deficient calorie intake, doing strenuous exercise, alcohol intake). Consider discontinuing treatment prior to or at the time of iodinated contrast imaging procedure in patients with eGFR of 30-60 mL/min/1.73 m2 or history of hepatic impairment, alcoholism, or heart failure; re-evaluate eGFR 48 hours after the procedure and restart therapy if renal function is stable. Not indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis. Debilitated or malnourished patients. Hepatic and mild to moderate renal impairment. Elderly. Pregnancy and lactation.
Obtain plasma glucose (frequency depends on individual treatment regimen, hypoglycaemia risk, and other patient-specific factors); HbA1c (twice yearly for those with stable glycaemic control and are meeting treatment goals; quarterly for those who have not met the treatment goals or with change in treatment). Monitor renal function (before and annually during treatment), haematologic parameters (annually), volume status (e.g. electrolytes, haematocrit, blood pressure), and vitamin B12 serum concentrations.
Overdosage
Symptoms: Hypoglycaemia or severe hypoglycaemic reactions with coma, seizure, or other neurological impairment; lactic acidosis. Management: Aggressive treatment with oral glucose and adjustment in drug dosage and/or meal patterns for mild hypoglycaemia without loss of consciousness or neurological findings. In case of diagnosed or suspected hypoglycaemic coma, administer rapid IV inj of concentrated (50%) glucose solution followed by a continuous infusion of a more dilute (10%) glucose solution at a rate that will maintain the blood glucose at a level above 100 mg/dL. Haemodialysis may be useful for the removal of the accumulated drug in suspected metformin overdosage.
Drug Interactions
Increased risk of hypoglycaemia with other glucose-lowering drugs. May decrease therapeutic effect with thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, oral contraceptives, estrogen, nicotinic acid, phenytoin, sympathomimetics, Ca channel blockers, and isoniazid.
Glipizide: Enhanced hypoglycaemic action with NSAIDs, certain azoles, sulfonamides, chloramphenicol, salicylates, coumarins, probenecid, MAOIs, and β-blockers. May decrease exposure with colesevelam; administer at least 4 hours before colesevelam.
Metformin: Intravascular administration of iodinated contrast agents may cause acute decrease in renal function, leading to accumulation of metformin and increased risk of lactic acidosis. May increase the risk of lactic acidosis with carbonic anhydrase inhibitors (e.g. topiramate, zonisamide, acetazolamide). Increased plasma concentration with nifedipine, furosemide, and organic cationic transporter-2 (OCT2)/multidrug and toxin extrusion (MATE) inhibitors (e.g. ranolazine, cimetidine, vandetanib, dolutegravir).
Food Interaction
Metformin: Increased risk of lactic acidosis with alcohol.
Action
Description: Mechanism of Action: Glipizide, a sulfonylurea antidiabetic agent, stimulates insulin release from pancreatic β-cells, decreases glucose output from the liver, and increases insulin sensitivity at peripheral target sites.
Metformin, a biguanide antidiabetic agent, reduces the production of hepatic glucose, decreases intestinal glucose absorption, and improves insulin sensitivity by increasing peripheral glucose uptake and utilisation. Pharmacokinetics: Absorption: Glipizide: Readily absorbed from the gastrointestinal tract. Bioavailability: 90-100%. Time to peak plasma concentration: 1-3 hours.
Metformin: Slowly and incompletely absorbed from the gastrointestinal tract. Absolute bioavailability: Approx 50-60% (fasting state). Time to peak plasma concentration: 2-3 hours. Distribution: Glipizide: Plasma protein binding: 98-99%, mainly to albumin.
Metformin: Crosses the placenta; enters breast milk (small amounts). Volume of distribution: 654 ± 358 L. Metabolism: Glipizide: Metabolised mainly in the liver by CYP2C9 isoenzyme into inactive metabolites. Excretion: Glipizide: Mainly via urine (80% as metabolites, <10% as unchanged drug); faeces (10%). Elimination half-life: 2-5 hours.
Metformin: Via urine (90% as unchanged drug). Elimination half-life: 4-9 hours (plasma); approx 17.6 hours (blood).
Chemical Structure
Glipizide Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 3478, Glipizide. https://pubchem.ncbi.nlm.nih.gov/compound/Glipizide. Accessed Feb. 27, 2023.
Metformin Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 4091, Metformin. https://pubchem.ncbi.nlm.nih.gov/compound/Metformin. Accessed Feb. 27, 2023.
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