Is gliclazide (sulfonylurea) 60 mg a suitable addition for a patient with type 2 diabetes mellitus (T2DM) already on metformin (biguanide) with an Hemoglobin A1c (HbA1c) greater than 6.1%?

Gliclazide 60 mg as Add-On Therapy for T2DM with HbA1c >6.1%

Yes, gliclazide 60 mg is a suitable addition to metformin for patients with T2DM and HbA1c >6.1%, though newer agents like GLP-1 receptor agonists or SGLT2 inhibitors should be prioritized if the patient has cardiovascular disease, heart failure, or chronic kidney disease. 1

When to Add Gliclazide to Metformin

Metformin remains the foundation of therapy, and when HbA1c exceeds target on metformin alone, a second agent should be added within 3-6 months. 1 The choice depends on specific patient characteristics:

Prioritize Other Agents First If:

• Established atherosclerotic cardiovascular disease exists: Use GLP-1 receptor agonist or SGLT2 inhibitor instead of gliclazide 1
• Heart failure is present or patient is at high risk: SGLT2 inhibitors are preferred 1
• Chronic kidney disease exists: Consider SGLT2 inhibitors or GLP-1 receptor agonists for renal protection 1
• Weight loss is a priority: GLP-1 receptor agonists cause weight loss, while gliclazide causes weight gain 1

Gliclazide Is Appropriate When:

• Cost is a major concern: Sulfonylureas like gliclazide are inexpensive compared to newer agents 1
• Patient lacks cardiovascular disease, heart failure, or significant CKD: In this scenario, gliclazide is a reasonable second-line option 1
• Rapid HbA1c reduction is needed: Gliclazide can reduce HbA1c by approximately 1% 1

Dosing Strategy for Gliclazide

Start with gliclazide modified-release 30 mg once daily, titrating at monthly intervals to 60 mg, then 120 mg if needed to achieve glycemic targets. 2 The modified-release formulation provides 24-hour coverage with once-daily dosing, improving compliance. 2

• Gliclazide 60 mg modified-release once daily is the most commonly prescribed dose in clinical practice 3
• Maximum dose is 120 mg daily for modified-release formulation 2
• For immediate-release gliclazide, 80 mg twice daily is the typical starting regimen 3

Expected Efficacy

Real-world evidence from India demonstrates that gliclazide added to metformin reduces HbA1c by approximately 1.4% in patients with baseline HbA1c >7%. 3 Specifically:

• Gliclazide monotherapy reduces HbA1c by 0.8-1.6% depending on baseline values 2, 3
• Gliclazide plus metformin combination reduces HbA1c by 1.4-1.6% 3, 4
• The combination achieves HbA1c <7% in approximately 36% of patients previously uncontrolled on sulfonylurea alone 4

Critical Safety Considerations

Hypoglycemia risk is the primary concern with gliclazide, though it is lower than with other sulfonylureas. 1

• Avoid gliclazide in patients at high risk for hypoglycemia: elderly patients, those with advanced CKD stages 4-5, patients with limited life expectancy, or those with history of severe hypoglycemia 5
• In the ADVANCE trial using gliclazide, hypoglycemia rates were lower than with insulin or other sulfonylureas 1
• Weight gain of 1-2 kg typically occurs with sulfonylurea therapy 1
• No dose adjustment needed for mild-moderate renal impairment, but use caution in severe renal disease 1

Monitoring Requirements

Recheck HbA1c after 3 months to determine if the target is achieved; if HbA1c remains >7%, intensify therapy by adding a third agent or switching to insulin. 1, 5

• Monitor for hypoglycemia symptoms, especially during dose titration 2
• Assess renal function periodically, as both metformin and any future SGLT2 inhibitor additions require dose adjustment if kidney function declines 5
• Continue HbA1c monitoring every 3 months until target achieved, then every 6 months once stable 5

Important Caveats

The 2018 ADA/EASD consensus prioritizes agents with proven cardiovascular benefits over sulfonylureas when cardiovascular disease or risk factors are present. 1 While gliclazide was used in the ADVANCE trial and showed cardiovascular safety, it did not demonstrate the cardiovascular risk reduction seen with GLP-1 receptor agonists and SGLT2 inhibitors. 1

For patients with HbA1c significantly above target (>9%), consider initial dual therapy with metformin plus a more potent agent like a GLP-1 receptor agonist or basal insulin rather than gliclazide. 5, 6 Gliclazide is most appropriate when HbA1c is modestly elevated (7-9%) and cost or access to newer agents is limiting. 1