In an adult patient with type 2 diabetes on insulin, who is not pregnant and has no contraindications such as severe renal impairment, advanced heart failure, active liver disease, or recurrent severe hypoglycaemia, can metformin and gliclazide be added?

Can Metformin and Gliclazide Be Continued in Insulin-Requiring Patients?

Yes, both metformin and gliclazide can and should be continued when insulin is initiated in patients with type 2 diabetes, unless specific contraindications exist. 1

Core Guideline Recommendation

Glucose-lowering agents should be continued upon initiation of insulin therapy (unless contraindicated or not tolerated) for ongoing glycemic and metabolic benefits including weight, cardiometabolic, and kidney benefits. 1 This represents a strong recommendation (Grade A) from the 2024 American Diabetes Association Standards of Care. 1

Metformin Continuation

• Metformin must be continued as long as it is tolerated and not contraindicated, with other agents (including insulin) added to metformin rather than replacing it. 1, 2

• Metformin is safe to continue with eGFR ≥30 mL/min/1.73 m², though dose reduction to approximately 50% of maximum is required when eGFR is 30-44 mL/min/1.73 m². 1, 2

• Metformin provides ongoing benefits beyond glycemic control, including potential cardiovascular risk reduction and weight neutrality that counterbalances insulin-associated weight gain. 1

• The only absolute contraindications are advanced renal insufficiency (eGFR <30 mL/min/1.73 m²), decompensated cirrhosis (Child-Pugh class B-C), and acute conditions causing tissue hypoperfusion. 1, 2

Gliclazide (Sulfonylurea) Management

When starting insulin therapy, the dose of sulfonylureas like gliclazide should be reassessed and potentially reduced to minimize hypoglycemia risk and treatment burden, but complete discontinuation is not mandatory. 1

• The 2024 ADA guidelines specifically state to "reassess the need for and/or dose of glucose-lowering agents with higher hypoglycemia risk (i.e., sulfonylureas and meglitinides)" when initiating insulin. 1

• Gliclazide can be continued at a reduced dose if additional glycemic benefit is needed, particularly in patients not yet at glycemic target. 3

• In older adults or those with complex medical conditions, intensive glycemic management with both insulin and sulfonylureas has been identified as potential overtreatment and should prompt consideration of de-intensification. 1

Practical Algorithm for Insulin Initiation

When adding insulin to metformin plus gliclazide:

1. Continue metformin at current dose (unless eGFR <30 or other contraindication exists). 1, 2

2. Reduce gliclazide dose by 50% to minimize hypoglycemia risk while maintaining some sulfonylurea benefit. 1

3. Start basal insulin at conservative dose (0.1-0.2 units/kg/day). 1

4. Titrate insulin based on fasting glucose, targeting 90-150 mg/dL (5.0-8.3 mmol/L) in most adults. 1

5. Monitor for hypoglycemia closely, particularly during the first 2-4 weeks. 1

6. Consider discontinuing gliclazide entirely if basal insulin dose exceeds 0.5 units/kg/day (sign of overbasalization) or if recurrent hypoglycemia occurs. 1

Critical Caveats and Pitfalls

• Do not automatically discontinue all oral agents when starting insulin—this outdated practice eliminates the metabolic benefits of metformin and may require higher insulin doses. 1

• Watch for overbasalization: if basal insulin exceeds 0.5 units/kg/day with persistent hyperglycemia, the issue is likely inadequate prandial coverage, not insufficient basal insulin, and adding more basal insulin while continuing gliclazide will increase hypoglycemia risk. 1

• In older adults with limited life expectancy or complex medical conditions, the combination of insulin plus sulfonylurea represents high-risk overtreatment and simplification should be strongly considered. 1

• Hypoglycemia risk is substantially higher when sulfonylureas are combined with insulin compared to metformin plus insulin, requiring patient education on recognition and treatment of hypoglycemia. 1

When to Discontinue Gliclazide

Discontinue gliclazide if:

• Recurrent hypoglycemia occurs (≥2 episodes per week with blood glucose <70 mg/dL). 1
• Patient achieves HbA1c <6.5% on insulin plus metformin alone. 1
• Basal insulin dose exceeds 0.5 units/kg/day, suggesting overbasalization. 1
• Patient is elderly (≥80 years) with limited life expectancy (<10 years) or complex medical conditions. 1