What are the side effects of Gliclazide?

Gliclazide Side Effects

Gliclazide has a notably low incidence of hypoglycemia and weight gain compared to other sulfonylureas, making it one of the safer options in this drug class. 1

Primary Side Effects

Hypoglycemia

• Hypoglycemia occurs less frequently with gliclazide than with other sulfonylureas due to its specific effect on restoring the first-phase insulin response, which creates a more physiologic insulin secretion pattern 2, 1
• The modified-release (MR) formulation provides 24-hour glycemic control with even lower hypoglycemia risk than the immediate-release formulation 3
• Risk increases substantially (approximately 50%) when gliclazide is combined with DPP-4 inhibitors 4
• When combined with insulin or other insulin secretagogues, hypoglycemia risk increases further and requires dose reduction of gliclazide 4

Weight Gain

• Weight gain is minimal with gliclazide and is not considered a major clinical problem 3
• This contrasts with other sulfonylureas where weight gain of approximately 2 kg is common 5
• The lower weight gain profile is attributed to gliclazide's specific pattern of insulin release restoration 2

Less Common Side Effects

Gastrointestinal Effects

• Gastrointestinal side effects can occur but are generally mild 1
• Starting with low doses and titrating gradually minimizes these effects 5

Cardiovascular Considerations

• Cardiovascular outcome studies show no evidence of increased cardiovascular events with gliclazide 3
• Dizziness, nervousness, and syncope are listed as potential cardiovascular side effects for the sulfonylurea class 4
• Unlike some other sulfonylureas, gliclazide has beneficial effects on platelet function and may actually reduce progression of diabetic microangiopathy 2, 6

Special Population Warnings

Elderly Patients

• Gliclazide MR is preferred among sulfonylureas for elderly patients due to superior hypoglycemia safety profile 7
• Frequency of hypoglycemia should be monitored at each visit in older adults 5

Renal Impairment

• Gliclazide undergoes extensive hepatic metabolism with only 4% renal clearance, making it safer than many sulfonylureas in mild-to-moderate renal impairment 2
• However, for patients with significant chronic kidney disease, glipizide is the preferred sulfonylurea as it lacks active metabolites entirely 8, 7

Drug Interactions

High-Risk Combinations

• Antimicrobials (fluoroquinolones and sulfamethoxazole-trimethoprim) increase effective gliclazide dose and may precipitate hypoglycemia; temporary dose reduction or discontinuation should be considered 5
• DPP-4 inhibitors increase hypoglycemia risk by 50% when added to gliclazide 4
• GLP-1 receptor agonists increase hypoglycemic potential when combined with gliclazide 4

Clinical Pearls for Minimizing Side Effects

Dosing Strategy

• Start with low doses (40-80 mg/day) and titrate based on glycemic response 9
• Doses above 80 mg/day may not provide additional clinical benefit in many patients 9
• Take at the main mealtime for once-daily dosing 5

Monitoring and Adjustments

• Consider temporary discontinuation during acute illness, procedures with iodinated contrast, or when high-risk antimicrobials are prescribed 5
• Patient education on recognizing and treating hypoglycemia is essential 5
• Self-monitor blood glucose closely during the first 3-4 weeks after initiation or dose changes 5

Comparative Safety Profile

Among second-generation sulfonylureas, gliclazide has lower hypoglycemia risk than both glimepiride and glyburide 7, with glyburide being explicitly contraindicated in elderly patients due to prolonged hypoglycemia risk 8. The overall tolerability profile of gliclazide, combined with its low incidence of hypoglycemia and minimal weight gain, positions it favorably within the sulfonylurea class 1.