Glipizide for Adult Type 2 Diabetes
Primary Indication
Glipizide is a second-generation sulfonylurea indicated for adults with type 2 diabetes mellitus when glycemia is not controlled by diet and exercise alone. 1 It works primarily by potentiating insulin action and increasing nutrient-stimulated insulin secretion from pancreatic beta-cells. 1
Dosing Strategy
Initial Dosing
- Start at 5 mg once daily in newly diagnosed patients with type 2 diabetes 2
- For elderly, debilitated, or renally/hepatically impaired patients: start at 2.5 mg once daily 2
- The immediate-release formulation should be taken 30 minutes before meals to optimize absorption 1
Titration Protocol
- Titrate at 1- to 2-week intervals based on glycemic response 3
- Usual maintenance range: 5–15 mg daily 1
- Maximum dose: 40 mg daily (though efficacy plateaus above 15–20 mg) 1
- Doses above 15 mg should be divided into two daily doses 1
Extended-Release Formulation (GITS)
- Start at 5 mg once daily with breakfast 4
- Titrate to 10–20 mg once daily as needed 4
- Provides more stable plasma concentrations and may improve compliance with once-daily dosing 4
Contraindications
Absolute Contraindications
- Type 1 diabetes mellitus 1
- Diabetic ketoacidosis 1
- Significant liver disease 1
- Significant kidney disease 1
- Known hypersensitivity to sulfonylureas 1
Relative Cautions
- Elderly patients require careful dose selection due to diminished counter-regulatory hormone responses to hypoglycemia 3
- Renal impairment necessitates conservative initiation at 0.5–1 mg daily with slow titration 3
Adverse Effects
Hypoglycemia (Most Important)
- Occurs in 10–20% of patients on monotherapy for ≤1 year 5
- Occurs in ≥50% of patients receiving concomitant insulin for 6 months 5
- Risk factors include: elderly age, renal impairment, drug interactions, and inadequate caloric intake 3
- Glipizide (shorter-acting) is preferred over glyburide (longer-acting) in older adults to minimize hypoglycemia risk 6, 3
Drug Interactions Precipitating Hypoglycemia
- Fluoroquinolones and sulfamethoxazole-trimethoprim increase effective glipizide dose 6, 3
- Temporarily reduce or discontinue glipizide when these antimicrobials are prescribed 6, 3
Other Adverse Effects
- Gastrointestinal symptoms (nausea, diarrhea) – mitigated by starting with low doses 3
- Weight gain – common with all sulfonylureas 1
- Cardiovascular effects – glipizide has fewer and less severe cardiovascular effects than glyburide 5
Combination Therapy
With Insulin
- Indicated for patients with secondary sulfonylurea failure (inadequate response to sulfonylureas alone) 5, 7
- Reduce glipizide dose by 50% or discontinue entirely when adding insulin to prevent severe hypoglycemia 3
- In one study, insulin + glipizide reduced fasting plasma glucose from 8.7 to 6.8 mmol/L and lowered total daily insulin dose from 87.3 to 69.1 units 7
- Glycated hemoglobin improved from 11.4% to 9.8% with combination therapy 7
With Other Oral Agents
- Glipizide may be combined with metformin or other oral antidiabetic drugs, though specific efficacy data require further study 5
Monitoring Requirements
Initial Phase (First 3–4 Weeks)
- Self-monitor blood glucose levels closely after any medication changes 3
- Assess for hypoglycemia at each visit, especially in elderly patients 6, 3
Ongoing Monitoring
- Glycated hemoglobin (HbA1c) every 3 months until target achieved, then every 6 months 6
- Fasting plasma glucose to guide dose adjustments 1
- Frequency of hypoglycemia should be documented at every visit 6
Special Populations
Elderly Patients
- Glipizide is preferred over glyburide due to shorter duration of action and lower hypoglycemia risk 6, 3
- Start at 2.5 mg daily and titrate slowly 3, 2
- Monitor hypoglycemia frequency at each visit 6
Renal or Hepatic Impairment
- Start at 0.5–1 mg daily with slow titration 3
- Pharmacokinetics are mainly unaltered in mild-to-moderate renal or liver disease, but caution is warranted 5
- Significant renal or hepatic disease is a contraindication 1
Clinical Pearls and Pitfalls
Common Pitfalls
- Do not use glyburide in older adults—it has a longer duration of action and higher hypoglycemia risk 6
- Do not overlook antimicrobial interactions—fluoroquinolones and trimethoprim-sulfamethoxazole can precipitate severe hypoglycemia 6, 3
- Do not continue full-dose glipizide when adding insulin—reduce by 50% or discontinue to avoid hypoglycemia 3
Comparative Safety
- Newer agents (SGLT2 inhibitors, GLP-1 agonists) have lower rates of severe hypoglycemia and serious adverse events compared to sulfonylureas 3
- Consider newer agents first-line in patients at high cardiovascular or renal risk, per current guidelines 6
Efficacy Considerations
- Greatest glucose-lowering effect occurs in the first 4 hours after dosing 5
- Glipizide reduces blood glucose more rapidly than glipizide over the first few weeks of treatment 5
- Efficacy plateaus between 4 and 8 mg/day—little additional benefit above this range 5
When to Reassess or Discontinue
- Reassess medication regimen every 3–6 months and adjust as needed 6
- Discontinue if secondary failure occurs (loss of glycemic control despite maximum dose) and consider adding insulin or switching to another agent class 6, 5
- Stop immediately if severe hypoglycemia, allergic reaction, or significant hepatic/renal dysfunction develops 1