Glipizide

Key points

• People with glucose 6-phosphate dehydrogenase (G6PD) deficiency are at risk of haemolytic anaemia when treated with glipizide or another sulfonylurea, and the Summary of Product Characteristics suggests a non-sulfonylurea alternative should be considered for this group.
• Glipizide’s mean total body clearance is about 3 litres per hour after a single intravenous dose in adults with type 2 diabetes, and it is eliminated mainly through hepatic biotransformation, with less than a tenth of a dose excreted unchanged in urine or faeces.
• The most common adverse reactions reported for glipizide, each above three percent incidence, are dizziness, diarrhoea, nervousness, tremor, hypoglycaemia and flatulence.

How it works

Glipizide primarily lowers blood glucose by stimulating insulin release from the pancreas, an effect that depends on functioning beta cells in the pancreatic islets. Sulfonylureas, including glipizide, bind to the sulfonylurea receptor on the pancreatic beta cell membrane, closing an ATP sensitive potassium channel and so triggering insulin release. The Summary of Product Characteristics for Minodiab adds that stimulation of insulin secretion by glipizide in response to a meal is of major importance, and that fasting insulin levels are not raised even with long term use, while the after meal insulin response continues to be enhanced after at least six months of treatment.

Safety specific to Glipizide

All sulfonylureas, including glipizide, are capable of producing severe hypoglycaemia, and combining glipizide with other antidiabetic medication can increase that risk. The Summary of Product Characteristics notes that hypoglycaemia can be harder to recognise in elderly patients and in those taking beta blocking drugs, and that it is more likely when calorie intake is low, after severe or prolonged exercise, when alcohol has been taken, or when more than one glucose lowering medicine is used.

Sulfonylureas including glipizide can cause haemolytic anaemia in people with glucose 6-phosphate dehydrogenase (G6PD) deficiency, and the US label advises avoiding glipizide in this group; the Summary of Product Characteristics adds that a non-sulfonylurea alternative should be considered for these patients. Postmarketing reports also describe haemolytic anaemia in some patients without known G6PD deficiency.

The label reports that oral hypoglycaemic drugs have been associated with increased cardiovascular mortality against treatment with diet alone or diet plus insulin, a warning based on the University Group Diabetes Program study, a long term trial in 823 patients with type 2 diabetes randomly assigned to one of four treatment groups.

Because the extended release tablet does not dissolve, the label reports obstructive symptoms in patients with known strictures who took another drug with this same non-dissolvable extended release formulation, and it advises avoiding glipizide in patients with pre-existing severe gastrointestinal narrowing, whether from disease or from an earlier procedure.

Glipizide is contraindicated together with miconazole under the Summary of Product Characteristics, and the US label advises close monitoring for hypoglycaemia when glipizide is combined with either miconazole or fluconazole, since fluconazole raises plasma concentrations of glipizide in a way that may lead to hypoglycaemia.

The Summary of Product Characteristics states that glipizide is contraindicated in pregnancy, while the US label notes that sulfonylureas including glipizide cross the placenta and have been associated with neonatal hypoglycaemia, and advises that glipizide should be discontinued at least two weeks before expected delivery.

Blood glucose control with glipizide can also be lost temporarily during physical stress such as fever, trauma, infection or surgery, and the Summary of Product Characteristics notes that the glucose lowering effect of oral hypoglycaemic drugs generally, including glipizide, can lessen in many patients over time as diabetes progresses or responsiveness to the drug diminishes.

Further reading

• GLUCOTROL XL- glipizide tablet, extended release
• Glipizide: MedlinePlus Drug Information
• Minodiab 5mg Tablets