For a 71‑year‑old woman with hemoglobin A1c 6.7% taking metformin 500 mg, glimepiride 2 mg, and empagliflozin 5 mg/metformin 500 mg (Synjardy), which medication(s) should be reduced or discontinued to minimize hypoglycemia risk?

Discontinue Glimepiride to Minimize Hypoglycemia Risk

For this 71-year-old woman with an A1C of 6.7% on triple therapy (metformin, glimepiride, and Synjardy), glimepiride should be discontinued immediately as she is overtreated and at high risk for hypoglycemia. 1, 2

Rationale for Glimepiride Discontinuation

Patient is Overtreated

• An A1C of 6.7% is substantially below the recommended target of <7.5% for healthy older adults and <8.0% for those with complex health status. 1
• A1C levels below 6.5% should prompt stopping or reducing medications associated with hypoglycemia risk. 1
• This patient meets criteria for deintensification: she is a 71-year-old on multiple glucose-lowering agents with A1C well below target, placing her at unnecessary hypoglycemia risk. 1, 2

Glimepiride Has the Highest Hypoglycemia Risk

• Sulfonylureas like glimepiride should be discontinued first when addressing hypoglycemia risk because they stimulate insulin secretion regardless of blood glucose levels. 2, 3
• Glimepiride provides minimal cardiovascular or renal benefits compared to her other medications. 2
• In the head-to-head comparison, empagliflozin (component of Synjardy) caused hypoglycemia in only 2% of patients versus 24% with glimepiride at 104 weeks. 4

Synjardy Provides Superior Protection

• Synjardy (empagliflozin/metformin combination) should be continued as it provides cardiovascular and renal protection with minimal hypoglycemia risk. 1, 4
• The empagliflozin component reduces cardiovascular death, renal events, and heart failure hospitalization. 1
• This combination has demonstrated superior glycemic control compared to glimepiride when added to metformin, with significantly lower hypoglycemia rates. 4

Medications to Continue

Metformin (500 mg standalone + 500 mg in Synjardy)

• Metformin should always be continued in older adults as it has the lowest hypoglycemia risk among oral agents and provides cardiovascular benefits. 2, 5
• It does not cause hypoglycemia when used alone. 5
• Safe to use with eGFR ≥30 mL/min/1.73 m². 1, 5

Synjardy (Empagliflozin 5 mg/Metformin 500 mg)

• Continue this combination for its cardio-renal protective effects independent of glycemic control. 1
• The SGLT2 inhibitor component (empagliflozin) has proven cardiovascular benefit and minimal hypoglycemia risk. 1, 4

Expected Outcome After Glimepiride Discontinuation

• A1C may rise modestly (approximately 0.5-1.0%) but will likely remain at or below 7.5%, which is appropriate for a healthy 71-year-old. 1, 4
• Hypoglycemia risk will decrease dramatically from 24% to 2% based on comparative trial data. 4
• If A1C rises above 7.5% after discontinuation, the Synjardy dose can be increased or a GLP-1 receptor agonist added rather than restarting a sulfonylurea. 1

Critical Monitoring After Discontinuation

• Recheck A1C in 3 months to ensure glycemic control remains adequate (target <7.5% for healthy older adult). 1
• Monitor for symptoms of hyperglycemia (polyuria, polydipsia, fatigue) which would indicate need for alternative therapy. 6
• Assess renal function annually to ensure metformin and empagliflozin remain appropriate. 5

Common Pitfalls to Avoid

• Do not discontinue metformin first—it has the lowest hypoglycemia risk and should be maintained. 2, 5
• Do not reduce all medications simultaneously—this makes it impossible to identify the causative agent and can cause rebound hyperglycemia. 2
• Do not continue glimepiride simply because A1C is "controlled"—overtreatment with hypoglycemia-causing agents should be avoided even when A1C is at goal. 1
• Do not restart sulfonylureas if glycemic control worsens; instead, intensify with GLP-1 receptor agonists or increase Synjardy dose. 1