Monitor urine (glucose and ketones), FPG, HbA1c, and fructosamine; haematologic parameters (e.g. Hb/hematocrit, RBC indices), renal function; signs and symptoms of hypoglycemia; vit B12 levels.
Overdosage
Symptoms: Mild to severe hypoglycaemia which may lead to hypoglycaemic coma (glibenclamide); lactic acidosis (metformin). Management: Mild hypoglycaemia w/o loss of consciousness may be treated w/ oral glucose. Severe hypoglycaemic reactions w/ coma, seizure or other neurological impairment require immediate hospitalisation. Admin rapid IV inj of glucose 50% soln in case of hypoglycaemic coma. Haemodialysis may be useful for removal of accumulated drugs in metformin overdose.
Drug Interactions
Decreased hypoglycaemic effect w/ thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, oestrogen, OC, phenytoin, nicotinic acid, sympathomimetics, Ca channel blockers, isoniazid. Glipizide: Increased hypoglycaemic effect w/ NSAIDs and other highly protein bound drugs, salicylates, sulfonamides, chloramphenicol, probenecid, coumarins, MAOIs, β-blockers. Risk of severe hypoglycaemia w/ oral miconazole. Decreased plasma concentration w/ colesevelam. Metformin: Increased plasma concentration w/ furosemide, nifedipine and cimetidine. Potentially Fatal: Alteration of renal function w/ iodinated contrast materials.
Food Interaction
Avoid alcohol.
Action
Description: Glipizide stimulates insulin release from pancreatic β-cells, reduces glucose output from the liver and increases insulin sensitivity at peripheral target sites. Metformin reduces hepatic glucose production, decreases intestinal glucose absorption and improves insulin sensitivity by increasing peripheral glucose uptake and utilisation. Pharmacokinetics: Absorption: Glipizide: Readily absorbed from the GI tract. Time to peak plasma concentration: 1-3 hr. Metformin: Slowly and incompletely absorbed from the GI tract. Bioavailability: Approx 50-60%. Distribution: Glipizide: Plasma protein binding: Extensively bound (98-99%). Metformin: Crosses the placenta and enters breast milk (small amounts). Metabolism: Glipizide: Extensively metabolised in the liver. Metformin: Not metabolised in the liver. Excretion: Glipizide: Via urine, mainly as inactive metabolites. Half-life: Approx 2-4 hr. Metformin: Via urine, as unchanged drug. Elimination half-life: Approx 2-6 hr.
Chemical Structure
Glipizide Source: National Center for Biotechnology Information. PubChem Database. Glipizide, CID=3478, https://pubchem.ncbi.nlm.nih.gov/compound/Glipizide (accessed on Jan. 22, 2020)
Metformin Source: National Center for Biotechnology Information. PubChem Database. Metformin, CID=4091, https://pubchem.ncbi.nlm.nih.gov/compound/Metformin (accessed on Jan. 20, 2020)
Anon. Glipizide and Metformin. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 22/10/2015.Buckingham R (ed). Glipizide. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 22/10/2015.Buckingham R (ed). Metformin Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 22/10/2015.Glipizide and Metformin HCl Tablet, Film Coated (Heritage Pharmaceuticals Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 22/10/2015.