Glyburide/metformin

Action and Spectrum

Actions and Spectrum: 

glyburide stimulates insulin release from the pancreas, lowering blood glucose levels. It can cause hypoglycemia (low blood sugar) as a side effect, especially in patients with impaired kidney function. 

metformin is a biguanide medication that reduces glucose production and improves insulin sensitivity in peripheral tissues such as muscle and fat.

Drug Interaction

Adverse Reaction

Frequency not  defined 

Dermatologic reactions 

Heartburn 

Nausea/vomiting 

Hypoglycemia 

Black Box Warning

Black Box Warning: 

In patients with an eGFR range of 30-60 ml/min/1.73ml2 or a history of alcoholism, hepatic disease, or heart failure, discontinue the metformin while taking the contrast imaging procedure. The drug can also cause lactic acidosis. 

Contraindication / Caution

Contraindication/Caution: 

Contraindications for glyburide include: 

• Known hypersensitivity to sulfonylureas or sulfonamides 
• Type 1 diabetes mellitus 
• Diabetic ketoacidosis 

Contraindications for metformin include: 

• Known hypersensitivity to metformin or any of the ingredients in the medication 
• Severe renal impairment (eGFR <30 mL/min/1.73 m²) 
• Acute or chronic metabolic acidosis 
• Diabetic ketoacidosis 

Both medications should be used with caution in patients with the following: 

• Impaired kidney function 
• Liver disease 
• Adrenal or pituitary insufficiency 
• Hemolytic anemia 
• Vitamin B12 deficiency 
• G6PD deficiency 

Pregnancy / Lactation

Pregnancy consideration:  

glyburide and metformin are not indicated during pregnancy.  

Breastfeeding warnings:  

Lactating infants should be monitored for any side effects due to the medication of lactating females. 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies do not show fetal risks in the first or later trimester.        
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women        
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.       
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.        
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.        
• Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

glyburide:  

glyburide binds the beta cells in the pancreas to produce more insulin. It binds to specific receptors on the beta cells, which triggers events that ultimately result in insulin release. glyburide also helps reduce glucose production by the liver and increases glucose uptake by muscle cells. 

metformin:  

metformin is a biguanide medication that reduces the amount of glucose produced by the liver and improves the body’s sensitivity to insulin. By activating AMPK, metformin helps reduce glucose production by the liver and increase glucose uptake by muscle cells. 

Pharmacodynamics: 

glyburide: 

glyburide binds to specific receptors on the beta cells, triggering events that ultimately release insulin. glyburide also helps reduce glucose production by the liver and increases glucose uptake by muscle cells. By increasing insulin secretion and reducing glucose production, glyburide can help lower blood glucose levels in individuals with type 2 diabetes.  

metformin: 

By activating AMPK, metformin helps reduce glucose production by the liver and increase glucose uptake by muscle cells. Additionally, metformin may help improve insulin sensitivity and reduce inflammation, contributing to improved glycemic control in individuals with type 2 diabetes. 

Pharmacokinetics: 

The onset of action takes place in 2-3 hours 

Metabolites formed are 4-trans-hydroxy glyburide and 3-cis-hydroxy glyburide (active) 

Half-Life 

• For glyburide is around 10 hours 
• For metformin is around 6 hours 

Duration 

• glyburide: 24 hr 
• metformin: No data 

Protein Bound 

• 99% of protein is bound to glyburide 
• Minimal protein is bound to metformin 
• For the volume of distribution of glyburide, no studies are performed 
• metformin has a 650 L volume of distribution 

Metabolism 

• glyburide: Extensively, in the liver to less active metabolites 
• metformin: Not metabolized 

Elimination and Excretion 

• glyburide is excreted 50% in urine and 50% in bile  
• metformin is excreted in urine 90% 

Adminstartion

Administration: 

glyburide/metformin is a combination medication that comes in a tablet form and is taken through the mouth. The medication is usually taken with meals as it reduces the risk of gastrointestinal side effects.

Swallow the tablets completely with a full glass of water. Never chew, crush, or break the tablets, which may affect how the body absorbs the medication. Store the drug product in a cool, dry place away from light and moisture. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: glyburide/metformin Pronounced: GLYE-bure-ide-and-met-FOR-min 

Why do we use glyburide/metformin? 

glyburide/metformin is a combination medication for managing blood glucose levels in type 2 diabetic patients. Here are some reasons why glyburide/metformin may be prescribed: 

• Control of blood glucose levels: glyburide is a sulfonylurea medication that stimulates the pancreas to produce more insulin, while metformin decreases the amount of glucose produced by the liver. It also improves the body’s sensitivity to insulin. Together, these medications can help improve glycemic control in individuals with type 2 diabetes. 
• Convenience: Combining two medications in one pill can be more convenient for individuals needing multiple medications to manage their diabetes. 
• Lower cost: glyburide/metformin is generally less expensive than taking the two medications separately, making it a more affordable option for some individuals with diabetes. 
• Improved adherence: Taking one pill instead of two may improve adherence to the medication regimen, essential for achieving and maintaining optimal blood glucose control.