What are the side effects of glipizide (a sulfonylurea)?

Side Effects of Glipizide

Glipizide's most clinically significant side effects are hypoglycemia and weight gain, though it carries a lower risk of severe hypoglycemia compared to other sulfonylureas like glyburide. 1

Most Common and Clinically Important Side Effects

Hypoglycemia

• Hypoglycemia is the major adverse effect of glipizide, though severe episodes requiring assistance, coma, or seizure are infrequent 1
• Glipizide has a lower risk of hypoglycemia compared to other sulfonylureas (particularly glyburide and chlorpropamide), making it a preferred second-generation agent 1, 2
• Risk is substantially higher in elderly patients and those with renal impairment, requiring careful dose selection and monitoring 1
• Antimicrobials (fluoroquinolones and sulfamethoxazole-trimethoprim) interact with glipizide to increase effective dose and may precipitate hypoglycemia; temporary dose reduction or discontinuation should be considered 1

Weight Gain

• Weight gain of approximately 2 kg is common following initiation of glipizide therapy 1
• This weight gain is relatively modest compared to insulin or thiazolidinediones 1

Gastrointestinal Side Effects

• Gastrointestinal disturbances are the most common reactions overall 3
• Nausea and diarrhea occur in approximately 1 in 70 patients 3
• Constipation and gastralgia occur in approximately 1 in 100 patients 3
• These effects appear to be dose-related and may disappear with dose division or reduction 3

Neurological Side Effects

• Dizziness occurs in approximately 1 in 50 patients treated with glipizide 3
• Drowsiness and headache each occur in about 1 in 50 patients 3
• These symptoms are usually transient and seldom require discontinuance of therapy 3

Dermatologic Reactions

• Allergic skin reactions occur in about 1 in 70 patients, including erythema, morbilliform or maculopapular eruptions, urticaria, pruritus, and eczema 3
• These may be transient and disappear despite continued use; if persistent, discontinuation is warranted 3
• Porphyria cutanea tarda and photosensitivity reactions have been reported with sulfonylureas 3

Serious but Rare Adverse Effects

Hepatobiliary

• Cholestatic jaundice may occur rarely; glipizide should be discontinued if this occurs 3
• Cholestatic and hepatocellular forms of liver injury accompanied by jaundice have been reported rarely in post-marketing surveillance 3
• Occasional mild to moderate elevations of SGOT, LDH, alkaline phosphatase were noted 3

Hematologic

• Leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia, and pancytopenia have been reported with sulfonylureas 3
• These are extremely rare but require monitoring 3

Endocrine/Metabolic

• Cases of hyponatremia and syndrome of inappropriate antidiuretic hormone (SIADH) secretion have been reported 3
• Hepatic porphyria has been reported with sulfonylureas 3

Cardiovascular Considerations

• Dizziness/nervousness and syncope are listed as cardiovascular side effects of sulfonylureas 1
• Some observational studies raised concerns about adverse cardiovascular outcomes, though recent systematic reviews found no increase in all-cause mortality compared with other active treatments 1
• Glipizide has an extremely low incidence of disulfiram-like alcohol reactions 3

Special Population Warnings

Elderly Patients

• Sulfonylureas with shorter duration of action, such as glipizide, are preferred in older adults 1
• Frequency of hypoglycemia should be monitored at each visit 1
• Glyburide (longer-acting) should be avoided, but glipizide is acceptable with caution 1

Renal Impairment

• Glipizide is the preferred sulfonylurea in renal impairment because it lacks active metabolites 2
• Can be used with caution when eGFR is reduced; glyburide should be avoided 1

Clinical Pearls for Minimizing Side Effects

• Start with low doses and titrate slowly to minimize gastrointestinal side effects and hypoglycemia risk 1, 2
• Patient education and use of low or variable dosing can mitigate hypoglycemia risk 1
• Greatest caution is warranted for older patients and those with chronic kidney disease 1
• Consider temporary discontinuation during acute illness, procedures with iodinated contrast, or when antimicrobials are prescribed 1