For a 72-year-old man with type 2 diabetes on glibenclamide (sulfonylurea) and metformin twice daily, with HbA1c 7.4%, should the sulfonylurea be discontinued and what is the recommended next step in therapy?

Treatment Intensification for Type 2 Diabetes with HbA1c 7.4%

Discontinue glibenclamide immediately and add a GLP-1 receptor agonist to the existing metformin regimen. 1, 2

Rationale for Discontinuing Glibenclamide

• At age 72, this patient has multiple risk factors for severe hypoglycemia from sulfonylureas: advanced age (>65 years), likely presence of some degree of renal impairment, and potential cognitive changes. 3
• Metformin provides lower cardiovascular mortality compared with sulfonylurea therapy, making the sulfonylurea the expendable agent in this dual regimen. 1
• When insulin or other glucose-lowering agents are added to a regimen containing sulfonylureas, the sulfonylurea should be discontinued to prevent hypoglycemia. 1
• Glibenclamide (glyburide) is particularly problematic as a potent, long-acting agent that carries the highest hypoglycemia risk among sulfonylureas. 3

Optimize Metformin Dosing First

• Before adding any third agent, ensure metformin is at maximum effective dose: increase to 2000 mg daily (1000 mg twice daily with meals) if the patient is currently taking less. 1, 4, 2
• The maximum daily dose is 2550 mg in the U.S., though doses above 2000 mg provide minimal additional efficacy with poorer tolerability. 1
• Verify renal function: metformin should not be used if eGFR <30 mL/min/1.73m² and dose reduction should be considered when eGFR <45 mL/min/1.73m². 1

Add GLP-1 Receptor Agonist as Preferred Third Agent

• GLP-1 receptor agonists are the preferred injectable medication before insulin for patients needing additional glucose-lowering beyond oral agents. 1
• GLP-1 RAs provide HbA1c reduction of 0.6-0.8% when added to existing therapy, with additional benefits of weight loss and minimal hypoglycemia risk. 4, 2
• They have proven cardiovascular benefits in patients at high cardiovascular risk, which is relevant for a 72-year-old with diabetes. 1, 4
• Once-weekly formulations are available, reducing injection burden compared to daily insulin. 1

Alternative: Consider SGLT2 Inhibitor

• If GLP-1 receptor agonists are contraindicated or not tolerated, an SGLT2 inhibitor (empagliflozin or canagliflozin) provides both glycemic control and cardiovascular/renal protection. 1
• SGLT2 inhibitors reduce HbA1c by 0.5-0.8%, cause weight loss, and do not increase hypoglycemia risk when combined with metformin alone. 1
• Efficacy depends on renal function; initiation requires eGFR >45 mL/min/1.73m² per current regulatory approval. 1

Monitoring and Follow-up

• Reassess HbA1c after 3 months to determine if the target of <7.0% is achieved. 4, 2
• Monitor vitamin B12 levels periodically with long-term metformin use, especially if anemia or neuropathy develops. 1, 2
• If HbA1c remains >7% after 3-6 months on optimized dual therapy (metformin + GLP-1 RA or SGLT2 inhibitor), consider adding basal insulin. 1, 4

Critical Pitfalls to Avoid

• Do not continue glibenclamide when adding insulin if insulin becomes necessary—this dramatically increases severe hypoglycemia risk. 1
• Avoid therapeutic inertia: do not wait beyond 3 months to intensify therapy if HbA1c remains above target. 1, 4
• Do not discontinue metformin when adding other agents unless contraindicated—it should remain the foundation of therapy throughout treatment intensification. 1
• For this 72-year-old patient, consider whether a less stringent target of 7.5-8.0% is more appropriate if there is limited life expectancy, history of severe hypoglycemia, or extensive comorbidities—but this should be an active decision, not default therapeutic inertia. 1, 4