Glipizide (Glucotrol, Diabes, minidiab) is a second-generation sulfonylurea that is used in the treatment of patients with diabetes mellitus type 2.

Glipizide (Minidiab, Diabes) Uses:

• Treatment for diabetes mellitus type 2:

  • Use in individuals with type 2 diabetes mellitus as a supplement to diet and exercise to enhance glycemic control.

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Glipizide (Diabes, Minidiab) Dose in Adults:

Note:

This medicine can be used together with or instead of metformin for patients who do not respond well to metformin or are unable to take it.

When choosing a medicine to treat type 2 diabetes, the doctor should consider the patient's individual situation.

This includes things like how likely the medicine is to cause low blood sugar, other health problems the patient may have (like heart disease or kidney problems), how it might affect weight, how well it works, potential side effects, how it is taken, cost, and what the patient wants.

Compared to other medicines for diabetes that are not insulin, sulfonylureas have a higher risk of causing low blood sugar because of how they work. It is usually better to choose a shorter-acting sulfonylurea like glipizide if sulfonylurea is needed.

• Immediate-release glipizide tablets:

Start with 2.5 mg once a day, 30 minutes before eating (preferably before breakfast).

To increase the dose, follow the instructions on the medicine label. Usually, the dose is increased by 2.5 to 5 mg every few days until the right amount is found.

However, some doctors suggest waiting two to four weeks before increasing the dose, and then increasing it more slowly over one to two weeks.

If the once-a-day dose doesn't work, the dose can be given twice a day, 30 minutes before breakfast and 30 minutes before dinner. Doses greater than 15 mg/day should usually be split into two doses.

The most effective dose is 20 mg/day. Taking more than 20 mg/day has not been shown to work better, although the medicine label says that up to 40 mg/day is safe.

• Extended-release Glipizide Tablets:

In the beginning, take 2.5 to 5 mg by mouth with breakfast or the first meal of the day.

The dosage can be changed based on how well it controls blood sugar. In one study, the dose was increased by 5 to 10 mg once a week.

The most you should take in a day is 20 mg.

• Patients already maintained on glipizide who require hospitalization:

If a patient needs to go to the hospital, stop taking non-insulin diabetes medicine and start using insulin instead.

If the patient is stable and has good control of blood sugar, the doctor may consider using non-insulin diabetes medicine while in the hospital, as long as there are no reasons not to.

It's important to monitor the dosage closely and make any needed changes

Recommendations for Glipizide (Diabes) conversion :

• Extended-release glipizide is changed from immediate-release glipizide.:

  • You can take the full daily dose of the medicine once a day by switching to the equivalent dose of the extended-release tablet

• When switching from insulin to an instant-release form of glipizide:

Note:

It's important to monitor blood sugar levels when switching from insulin to Glipizide, but there are no clear guidelines for doing so. Here is a general recommendation:

• If the patient takes 20 units of insulin, they should stop taking insulin and start taking Glipizide at the usual dose.
• If the patient takes more than 20 units of insulin, they can start taking Glipizide at the usual dose and gradually reduce the insulin dose based on how the patient responds.

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Glipizide Use in Children:

Not indicated.

Glipizide Pregnancy Risk Category: C

Newborns whose mothers took sulfonylureas during delivery have experienced severe hypoglycemia for 4-10 days. High blood sugar levels in women with diabetes can harm the baby, causing birth defects.

It is important for pregnant women with diabetes to keep their blood sugar levels in a safe range. However, this should not cause low blood sugar levels. Pregnant women with diabetes should consider other medications instead of glipizide.

Glipizide should not be taken during pregnancy. Most manufacturers advise stopping it at least one month before the due date.

Use of Glipizide while breastfeeding

Data from two cases show that glipizide is not present in breast milk. However, the manufacturer warns that breastfeeding mothers should consider the risk of hypoglycemia in infants before deciding to continue taking the medication or to stop breastfeeding.

The mother's needs should also be considered when making this decision. Women with pre-existing diabetes may benefit from having a small snack before breastfeeding to decrease the risk of hypoglycemia. Breastfeeding is safe with any insulin type, and some oral medications such as glipizide can also be used.

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Glipizide (Diabes) Dose in Kidney Disease:

 

For patients with renal impairment, including those with ESRD, the extended-release formulation of glipizide is generally not recommended due to the risk of hypoglycemia.

If it is used, a low starting dose of 2.5mg once daily is recommended with close monitoring for hypoglycemia. In general, the immediate-release formulation of glipizide is preferred for patients with renal impairment. Dose titration should be done cautiously and according to the patient's response and renal function.

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Glipizide (Diabes) Dose in Liver Disease:

Both the immediate-release and extended-release formulations of glipizide have an initial recommended dose of 2.5mg once daily.

Maintenance doses for both formulations should be conservative to prevent hypoglycemia.

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Glipizide (Diabes) side effects;

• Cardiovascular:

  • Syncope

• Central Nervous System:

  • Dizziness
  • Nervousness
  • Anxiety
  • Depression
  • Hypoesthesia
  • Insomnia
  • Pain
  • Paresthesia
  • Drowsiness
  • Headache

• Dermatologic:

  • Diaphoresis
  • Pruritus
  • Eczema
  • Erythema
  • Maculopapular Rash
  • Morbilliform Rash
  • Skin Rash
  • Urticaria

• Endocrine & Metabolic:

  • Hypoglycemia
  • Increased Lactate Dehydrogenase

• Gastrointestinal:

  • Diarrhea
  • Flatulence
  • Dyspepsia
  • Vomiting
  • Constipation
  • Nausea
  • Abdominal Pain

• Hepatic:

  • Increased Serum Alkaline Phosphatase
  • Increased Serum AST

• Neuromuscular & Skeletal:

  • Tremor
  • Arthralgia
  • Leg Cramps
  • Myalgia

• Ophthalmic:

  • Blurred Vision

• Renal:

  • Increased Blood Urea Nitrogen
  • Increased Serum Creatinine

• Respiratory:

  • Rhinitis

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Contraindications to Glipizide (Diabes):

It is important to note that patients with a history of sulfonamide allergy may have an increased risk of developing an allergic reaction to sulfonylureas such as glipizide.

While there is no clear evidence of cross-reactivity, caution should be exercised when prescribing glipizide to these patients, and they should be closely monitored for any signs of allergic reaction.

Patients who experience symptoms such as rash, hives, or difficulty breathing while taking glipizide should seek medical attention immediately

Warnings and Precautions

• Cardiovascular mortality

While there have been some concerns about the potential increased risk of cardiovascular events with certain oral hypoglycemic medications, particularly in patients with pre-existing cardiovascular disease, the evidence is not conclusive.

The UKPDS 1998 study did not find an increased risk of cardiovascular mortality with the use of sulfonylureas, including glipizide, compared to diet and insulin alone.

However, other agents, such as metformin, GLP-1 receptor agonists, and SGLT2 inhibitors, have been shown to have cardiovascular benefits and may be preferred in patients with atherosclerotic heart disease.

It is important for patients to discuss their individual risks and benefits with their healthcare provider when considering oral hypoglycemic medications

• Hypoglycemia

It is important to monitor blood glucose levels closely and adjust medication dosages accordingly in these populations.

Additionally, patients should be educated on the signs and symptoms of hypoglycemia and how to properly manage it. In cases of severe hypoglycemia, emergency medical attention should be sought immediately.

• Allergy to sulfonamide ("sulfa")

It is important to note that while cross-reactivity between sulfonamide medications is possible, it is not fully understood and may not always occur.

Allergic reactions to sulfonamides can range from mild skin reactions to severe, life-threatening reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN).

In cases of severe reactions, some clinicians may choose to avoid the use of sulfonamide medications altogether. It is always important for patients to inform their healthcare providers of any medication allergies they may have.

• Glucose-6phosphate dehydrogenase(G6PD) deficiency

Sulfonylurea-induced hemolytic anemia may occur in patients with G6PD deficiency, which is an X-linked genetic disorder that results in a deficiency of the enzyme glucose-6-phosphate dehydrogenase.

This deficiency makes red blood cells more susceptible to oxidative damage, which can be triggered by certain medications, including sulfonylureas.

Therefore, patients with G6PD deficiency should be cautious when taking sulfonylureas and should discuss with their healthcare provider the use of alternative medications.

However, it is important to note that sulfonylureas have been used safely in patients with normal G6PD levels, and cases of hemolytic anemia in these patients are rare.

• Hepatic impairment

Patients with hepatic impairment may have reduced hepatic metabolism and clearance of sulfonylureas, leading to prolonged hypoglycemia. Dose adjustments may be necessary in these patients.

• Renal impairment

Patients with impaired renal function should be cautious when taking sulfonylurea medications. This is because sulfonylureas are primarily metabolized by the liver, but they are also eliminated from the body through the kidneys.

If a patient's kidneys are not functioning properly, the medication may build up in their body and increase the risk of hypoglycemia. Dose adjustments or the use of alternative medications may be necessary for these patients.

• Stress-related disorders:

It is generally not recommended to stop insulin therapy for patients with diabetes who are exposed to stressors such as trauma, fever, or infection.

Stress can cause an increase in blood glucose levels, and discontinuing insulin therapy can lead to uncontrolled hyperglycemia and potentially life-threatening complications such as diabetic ketoacidosis.

Instead, adjustments to the insulin dosage may be needed to help maintain appropriate glucose levels during periods of stress. It is important for patients to speak with their healthcare provider before making any changes to their insulin regimen.

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Glipizide: Drug Interaction

Risk Factor C (Monitor therapy)
Ajmaline	Sulfonamides might make ajmaline more harmful or poisonous.  In particular, there may be an elevated risk for cholestasis.
Alcohol (Ethyl)	Sulfonylureas may increase Alcohol's harmful or toxic effects (Ethyl).  There could be a flushing reaction.
Alpha-Lipoic Acid	May strengthen an anti-diabetic agent's hypoglycemic impact.
Aminolevulinic Acid (Topical)	Aminolevulinic Acid's photosensitizing impact may be enhanced by photosensitizing agents (Topical).
Androgens	Can make blood glucose lowering medications more effective at lowering blood sugar.  Danazol is an exception.
Antidiabetic Agents	Possibly makes hypoglycemia-associated agents more effective.
Beta-Blockers	Sulfonylureas' hypoglycemic impact might be strengthened.  Betablockers that are cardioselective  As the initial sign of hypoglycemia, tachycardia seems to be concealed by all beta-blockers.Beta-blockers used intravenously most likely carry a lesser risk than those used systemically.  Exceptions: Metipranol; Levobunol.
Carbocisteine	Sulfonylureas may intensify Carbocisteine's harmful or hazardous effects.  Particularly, sulfonylureas may intensify the negative effects of the  alcohol contained in liquid formulations of medicines containing carbocisteine.
Chloramphenicol (Systemic)	Sulfonylureas' metabolism might be slowed down.
Cimetidine	Sulfonylureas' serum levels might rise.
Clarithromycin	GlipiZIDE serum concentration can rise.
Cyclic Antidepressants	Sulfonylureas' hypoglycemic impact might be strengthened.
Dexketoprofen	Sulfonamides' harmful or poisonous effects could be amplified.
Direct Acting Antiviral Agents (HCV)	May strengthen an anti-diabetic agent's hypoglycemic impact.
Fibric Acid Derivatives	Sulfonylureas' hypoglycemic impact might be strengthened.
Guanethidine	May strengthen an anti-diabetic agent's hypoglycemic impact.
Herbs (Hypoglycemic Properties)	May intensify the hypoglycemic effects of agents associated with hypoglycemia.
Hyperglycemia-Associated Agents	May reduce an anti-diabetic agent's therapeutic efficacy.
Hypoglycemia-Associated Agents	May increase other hypoglycemia-associated agents' hypoglycemic effects.
Hypoglycemia-Associated Agents	The hypoglycemic effect of hypoglycemia associated agents may be strengthened by antidiabetic agents.
Indobufen	GlipiZIDE serum concentration can rise.
Lumacaftor	May lower the serum level of CYP2C9 substrates (High Risk with Inhibitors or Inducers).  The serum concentration of CYP2C9 Substrates may rise when taking lumacaftor (High Risk with Inhibitors or Inducers).
Maitake	Can make blood glucose lowering medications more effective at lowering blood sugar.
Miconazole (Oral)	.Sulfonylureas' hypoglycemic impact might be strengthened.  Miconazole (Oral) may raise Sulfonylurea serum concentrations.
Monoamine Oxidase Inhibitors	Can make blood glucose lowering medications more effective at lowering blood sugar.
Pegvisomant	Can make blood glucose lowering medications more effective at lowering blood sugar.
Porfimer	The photosensitizing effect of Porfimer may be strengthened by photosensitizing agents.
Posaconazole	May strengthen GlipiZIDE's hypoglycemic effects. Posaconazole may raise GlipiZIDE's serum levels.
Probenecid	Sulfonylureas may lessen their ability to attach to proteins. Sulfonylurea serum levels may rise in response to probenecid.
Prothionamide	Can make blood glucose lowering medications more effective at lowering blood sugar.
Quinolones	Can make blood glucose lowering medications more effective at lowering blood sugar.  Blood Glucose Lowering Agents' therapeutic impact may be lessened by quinolones.  In particular, the use of quinolones may result in a loss of blood sugar control if an agent is being used to treat diabetes.
RaNITIdine	Sulfonylureas' serum levels might rise.
Rifapentine	May lower the serum level of CYP2C9 substrates (High risk with Inducers).
Ritodrine	May reduce an anti-diabetic agent's therapeutic efficacy.
Salicylates	Can make blood glucose lowering medications more effective at lowering blood sugar.
Selective Serotonin Reuptake Inhibitors	Can make blood glucose lowering medications more effective at lowering blood sugar.
Sulfonamide Antibiotics	Sulfonylureas' hypoglycemic impact might be strengthened.
Thiazide and Thiazide-Like Diuretics	May reduce an anti-diabetic agent's therapeutic efficacy.
Verteporfin	Verteporfin's photosensitizing effect may be strengthened by photosensitizing agents.
Vitamin K Antagonists (eg, warfarin)	The anticoagulant action of Vitamin K antagonists may be increased by sulfonylureas.  Sulfonylureas may have a greater hypoglycemia effect when used with vitamin K antagonists.
Voriconazole	Sulfonylureas' serum levels might rise.
Risk Factor D (Consider therapy modification)
Dabrafenib	May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP2C9 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects).
Colesevelam	May decrease the serum concentration of GlipiZIDE. Management: Administer glipizide at least 4 hours prior to colesevelam.
Dipeptidyl Peptidase-IV Inhibitors	.Sulfonylureas' hypoglycemic impact might be strengthened. When starting treatment with a dipeptidyl peptidase-IV inhibitor, take into account lowering the dose of sulfonylurea and keep an eye out for hypoglycemia in patients.
Enzalutamide	May lower the serum level of CYP2C9 substrates (High risk with Inducers).  Treatment: Enzalutamide should not be used concurrently with CYP2C9 substrates that have a limited therapeutic index.  Enzalutamide use, like with the use of any other CYP2C9 substrate, should be done with caution and under close observation.
Fluconazole	Sulfonylureas' serum levels might rise. Management: When possible, look for alternatives.  If fluconazole is started or the dose is increased, keep a cautious eye out for any increased or  decreased effects of sulfonylureas if the two medications are being used together.
Glucagon-Like Peptide-1 Agonists	Sulfonylureas' hypoglycemic impact might be strengthened. Management: When used with glucagonlike peptide-1 agonists, sulfonylurea dose reductions should be taken into account.
Metreleptin	Sulfonylureas' hypoglycemic impact might be strengthened.  Management: To reduce the risk for hypoglycemia when using metreleptin concurrently,  sulfonylurea dosage changes (including possibly significant decreases) may be necessary.  Observe carefully.
MiFEPRIStone	May increase the serum concentration of CYP2C9 Substrates (High risk with Inhibitors). Management: Use CYP2C9 substrates at the lowest recommended dose, and monitor closely for adverse effects, during and in the 2 weeks following mifepristone treatment.
RifAMPin	May decrease the serum concentration of Sulfonylureas. Management: Seek alternatives to these combinations when possible. Monitor closely for diminished therapeutic effects of sulfonylureas if rifampin is initiated/dose increased, or enhanced effects if rifampin is discontinued/dose decreased.
Sodium-Glucose Cotransporter 2 (SLGT2) Inhibitors	Sulfonylureas' hypoglycemic impact might be strengthened. When starting therapy with a sodium-glucose cotransporter 2 inhibitor, take into account lowering the dose of sulfonylurea and  keep an eye out for hypoglycemia in your patients.
Thiazolidinediones	Sulfonylureas' hypoglycemic impact might be strengthened.  Treatment: If a patient is taking thiazolidinediones, consider adjusting their sulfonylurea dosage and  keep an eye out for hypoglycemia.
Risk Factor X (Avoid combination)
Aminolevulinic Acid (Systemic)	Aminolevulinic Acid's photosensitizing impact may be enhanced by photosensitizing agents (Systemic).
Mecamylamine	The harmful or toxic effects of mecamylamine may be increased by sulfonamides.
Mitiglinide	May intensify the hazardous or harmful effects of sulfonylureas.

 

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Monitoring parameters:

• The signs of hypoglycemia include weakness, extreme hunger, excessive perspiration, and numbness in the limbs.
• Blood glucose
• In patients with stable glycemic control who are achieving their treatment objectives, hemoglobin A1c should be measured at least twice a year.
• Patients who have undergone therapy changes or who have not met these goals must take it every three months.
• Renal function
• Liver function
• Weight (due potential to cause weight gain

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How to administer Glipizide (Diabes)?

Important note: Patients who are not eating or have a low-calorie intake may need lower doses of medication to avoid low blood sugar levels.

Instant-release tablets: Take 30 minutes before a meal to reduce high blood sugar levels after eating. It's best to take it before breakfast if you only take it once a day.

Extended-release tablets: Take them with the first meal of each day. Don't split, chew, or crush the tablets, just swallow them

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Mechanism of action of Glipizide (Diabes):

This medication has three effects:

• It stimulates the pancreas to produce more insulin from beta cells.
• It decreases the liver's production of glucose.
• Peripheral target sites become more sensitive to insulin.

Duration:

• 12 to 24 hours

Absorption:

• Immediate release: Rapid and complete;
• delayed with food

Protein binding:

• 98% to 99%;
• primarily to albumin

Bioavailability:

• 90% to 100%

Metabolism:

• Hepatic via CYP2C9; forms inactive metabolites

Half-life elimination:

• 2 to 5 hours

Time to peak:

• 1 to 3 hours;
• extended-release tablets: 6 to 12 hours

Excretion:

• Urine (<10% as unchanged drug; 80% as metabolites);
• feces (10%)

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International Brand Names of Glipizide:

• glipiZIDE XL
• Glucotrol
• Glucotrol XL
• Actine
• Antidiab
• Apamid
• Brilizid
• Diabes
• Diacon
• Diactin
• Diasef
• Dibizide
• Digrin
• Dipazide
• Flumedil
• Gabaz
• Gipix
• Gipzide
• Glibenese
• Glibenese GITS
• Glibetin
• Glican
• Glidiab
• Glipid
• Glipimed
• Glipizide
• Glipizide BP
• Glipom
• Glix
• Glizide
• Gluco-Rite
• Glucodiab
• Glucolip
• Gluconil
• Glucotrol XL
• Glucozide
• Glupizide
• Gluzide
• Glygen
• Glynase
• Glyzip
• Luditec
• Meibida
• Melizid
• Melizide
• Mindiab
• Minibit
• Minidiab
• Minodiab
• Napizide
• Ozidia
• Pezide
• Singloben
• Sucrazide
• Sunglucon
• Topizide
• Xeltic

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Glipizide Brand Names in Pakistan:

Glipizide Tablets 5 mg
Gleezid	Pulse Pharmaceuticals
Glibense	Pfizer Laboratories Ltd.
Glipase	Pharmedic (Pvt) Ltd.
Minidiab	Pfizer Laboratories Ltd.