Diactin

Approved Indications:

• Type 2 Diabetes Mellitus (T2DM):
  • Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
  • May be used as monotherapy or in combination with other antidiabetic agents (e.g., metformin, insulin, DPP-4 inhibitors).

Clinically Accepted (Off-Label) Uses:

• Maturity-Onset Diabetes of the Young (MODY):
  • Specifically in patients with genetically confirmed HNF1A or HNF4A mutations.
• Gestational Diabetes Mellitus (GDM):
  • Occasionally used when insulin therapy is not feasible; however, not routinely recommended due to limited safety data.

Adults – Immediate-Release Tablets:

• Initial Dose: 5 mg once daily, taken 30 minutes before breakfast.
• Elderly or Sensitive Patients: Start with 2.5 mg once daily.
• Maintenance Dose: 2.5 mg to 20 mg daily, administered in 1 or 2 divided doses.
• Maximum Dose: 40 mg per day (doses >15 mg/day should be divided into two).

Adults – Extended-Release Tablets:

• Initial Dose: 5 mg once daily with breakfast.
• Titration: Increase by 2.5–5 mg at intervals based on blood glucose.
• Maximum Dose: 20 mg once daily.

Pediatrics:

• Not recommended. Safety and efficacy have not been established.

Renal Impairment:

• Use with caution. Start at the lowest effective dose (2.5 mg) and monitor glucose closely.

Hepatic Impairment:

• Dose adjustment recommended. Initiate at lower doses due to reduced hepatic metabolism.

Administration Notes:

• Take immediate-release tablets 30 minutes before meals.
• Do not crush or chew extended-release tablets.

Glipizide is a second-generation sulfonylurea that lowers blood glucose by stimulating insulin release from pancreatic beta cells. It binds to sulfonylurea receptors (SUR1) on ATP-sensitive potassium (K⁺ATP) channels of beta-cell membranes. This causes channel closure, cell depolarization, calcium influx, and insulin secretion. This insulin release is independent of current glucose levels, which increases the risk of hypoglycemia. Glipizide may also exert minor effects on enhancing peripheral insulin sensitivity.

• Absorption: Rapid and nearly complete (bioavailability >90%).
• Onset: Within 30 minutes (immediate-release).
• Peak Plasma Time: 1–3 hours (IR); 6–12 hours (ER).
• Distribution: Protein binding ~98–99%.
• Metabolism: Extensively metabolized in the liver via CYP2C9 to inactive metabolites.
• Half-life: 2–5 hours (IR); 7–14 hours (ER).
• Excretion: Primarily excreted via urine (mostly as metabolites); <10% unchanged.

• Pregnancy:
  • Classified as FDA Category C.
  • Animal studies have shown fetal harm; no well-controlled studies in pregnant women.
  • Insulin is the preferred treatment during pregnancy. Use only if clearly necessary.
• Lactation:
  • Excreted in small amounts in breast milk.
  • Risk of neonatal hypoglycemia is minimal but should be monitored.
  • Caution advised during breastfeeding.

• Primary Class: Oral Antidiabetic
• Subclass: Sulfonylurea (Second Generation)

• Hypersensitivity to glipizide, other sulfonylureas, or sulfonamides.
• Type 1 diabetes mellitus.
• Diabetic ketoacidosis (use insulin instead).
• Severe hepatic or renal dysfunction.
• Co-administration with bosentan (increased risk of liver toxicity).

• Hypoglycemia:
  • Risk is highest in elderly patients, those with renal/hepatic impairment, or poor nutritional intake.
  • Educate patients on early signs (sweating, tremor, dizziness).
• Cardiovascular Risk:
  • Long-term use may increase cardiovascular mortality (based on older sulfonylureas).
  • Use caution in patients with known cardiac disease.
• Weight Gain:
  • Common with long-term use.
• G6PD Deficiency:
  • Risk of hemolytic anemia.
• Stress Conditions (e.g., surgery, infection):
  • Consider temporary discontinuation and switch to insulin.
• Monitoring Required:
  • Fasting glucose, HbA1c, renal and hepatic function periodically.

Common Side Effects:

• Metabolic:
  • Hypoglycemia
  • Weight gain
• Gastrointestinal:
  • Nausea
  • Constipation
  • Diarrhea
• Neurological:
  • Dizziness
  • Headache
• Dermatologic:
  • Rash
  • Pruritus

Serious Adverse Effects:

• Severe hypoglycemia (seizures, coma)
• Hepatitis, cholestatic jaundice
• Hemolytic anemia, leukopenia, thrombocytopenia
• Photosensitivity
• Syndrome of inappropriate antidiuretic hormone secretion (SIADH) – rare

Major Drug-Drug Interactions:

• Increased Risk of Hypoglycemia:
  • Insulin, metformin, salicylates, MAO inhibitors, beta-blockers, sulfonamides, quinolones
• Reduced Glipizide Effectiveness:
  • Corticosteroids, diuretics, phenytoin, rifampin, oral contraceptives
• Enzyme Interactions:
  • Metabolized by CYP2C9
  • Inhibitors (e.g., fluconazole) increase risk of hypoglycemia
  • Inducers (e.g., rifampin) reduce effectiveness

Food & Alcohol Interactions:

• Food:
  • May delay absorption slightly; does not reduce overall efficacy.
• Alcohol:
  • Increases hypoglycemia risk
  • May cause disulfiram-like reactions (flushing, nausea)

• ADA Guidelines (Recent Years):
  • Recommend metformin or SGLT2 inhibitors/GLP-1 RAs as preferred first-line agents.
  • Sulfonylureas remain acceptable as second-line or cost-sensitive options.
• Guideline Preference:
  • Among sulfonylureas, glipizide is preferred over glyburide in elderly due to lower hypoglycemia risk.
• Formulary Updates:
  • ER formulations are increasingly favored due to better tolerability and once-daily convenience.

• Immediate-Release Tablets:
  • Store at room temperature (below 25°C or 77°F).
  • Protect from moisture and light.
• Extended-Release Tablets:
  • Store at 20°C to 25°C (68°F to 77°F).
  • Avoid humidity and freezing.
  • Keep in tightly closed containers.
• Special Instructions:
  • Do not crush or chew extended-release tablets.
  • Keep out of reach of children.
  • Dispose of expired or unused tablets safely.