What are the considerations for starting Synjardy XL (empagliflozin and metformin) in an elderly female patient with type 2 diabetes mellitus, currently taking glipiZIDE (glyburide) 10 MG Tablet, Januvia (sitagliptin) 50 MG Tablet, and Lantus (insulin glargine) at night, with blood glucose levels ranging from mild hyperglycemia to moderate hyperglycemia?

Discontinue Glipizide and Optimize Basal Insulin Before Adding Synjardy XL

In this elderly patient with suboptimal glycemic control (glucose 120-200 mg/dL) on glipizide, Januvia, and Lantus, you should first discontinue the glipizide to reduce hypoglycemia risk, then aggressively titrate the Lantus dose upward before considering Synjardy XL, as sulfonylureas should be discontinued once insulin is started and the current insulin dose appears inadequate. 1

Immediate Action: Discontinue Glipizide

• Sulfonylureas should be discontinued once insulin is started, as they contribute minimal additional benefit while substantially increasing hypoglycemia risk, especially when combined with insulin therapy. 1

• Glipizide is particularly problematic in elderly patients due to increased risk of hypoglycemia, bone loss, and fracture risk, and should be used with extreme caution if at all. 1

• The 2025 ADA guidelines specifically recommend that shorter-acting sulfonylureas like glipizide be monitored closely for hypoglycemia frequency at each visit, but emphasize caution in elderly populations. 1

• When any new glucose-lowering treatment is started and glycemic levels are close to target, ceasing or reducing medications with increased hypoglycemia risk is suggested. 1

Optimize Current Insulin Regimen First

• The current Lantus dose is likely subtherapeutic given the fasting glucose of 120 mg/dL (which should be <130 mg/dL) and overall glucose range of 120-200 mg/dL. 1

• Titrate Lantus upward by 2-4 units every 3-7 days based on fasting glucose values, targeting 80-130 mg/dL (or 90-150 mg/dL for elderly patients). 1

• A common starting dose for basal insulin is 10 units or 0.1-0.2 units/kg/day, suggesting the current dose may need significant upward adjustment. 1

• Monitor fasting blood glucose daily during titration to guide dose adjustments, and reduce insulin by 10-20% if hypoglycemia occurs. 1

Considerations for Adding Synjardy XL

Renal Function Assessment is Critical

• Metformin (component of Synjardy XL) may be used safely in individuals with eGFR ≥30 mL/min/1.73 m², while lower doses may be used in those with eGFR 30-45 mL/min/1.73 m². 1

• eGFR should be monitored every 3-6 months in elderly patients at risk for decline in kidney function. 1

• Metformin is contraindicated in advanced renal insufficiency and should be used with caution in those with impaired hepatic function or heart failure due to increased risk of lactic acidosis. 1

Benefits of Empagliflozin Component

• Empagliflozin (the SGLT2 inhibitor in Synjardy XL) provides cardiovascular and renal protection independent of glycemic control, with proven reduction in cardiovascular death and heart failure hospitalization. 2

• The combination of empagliflozin and metformin improves glucose control with minimal hypoglycemia risk (unless combined with insulin or insulin secretagogues), while reducing body weight and blood pressure. 3, 4

• Initial combination therapy with empagliflozin + metformin can reduce HbA1c by 1.9-2.1% in treatment-naïve patients, though this patient is already on multiple agents. 4

Special Elderly Patient Considerations

• Target HbA1c for elderly patients should be 7.5-8.0% rather than <7.0%, as tighter control increases hypoglycemia risk without demonstrated benefit in this population. 1

• Cost may be an especially important consideration, as elderly patients tend to be on many medications and live on fixed incomes. 1

• Empagliflozin is associated with higher rates of genital mycotic infections and potential for volume depletion-associated events, which require particular monitoring in elderly patients. 2

Recommended Treatment Algorithm

1. Immediately discontinue glipizide to eliminate hypoglycemia risk from sulfonylurea-insulin combination. 1

2. Continue Januvia 50 mg (appropriate dose for elderly or those with renal impairment), as DPP-4 inhibitors have few side effects and minimal hypoglycemia risk. 1

3. Aggressively titrate Lantus upward by 2-4 units every 3-7 days targeting fasting glucose 90-150 mg/dL for elderly patients. 1

4. Reassess glycemic control after 3 months of optimized basal insulin. 1

5. If HbA1c remains >7.5-8.0% after insulin optimization, then consider adding Synjardy XL, ensuring:

   • eGFR is ≥30 mL/min/1.73 m² (preferably ≥45 for full metformin dose) 1
   • Patient can afford the medication 1
   • Patient is counseled on genital hygiene and volume depletion signs 2

Critical Monitoring Points

• Monitor fasting blood glucose daily during insulin titration to guide adjustments. 1

• Check for hypoglycemia symptoms at every visit, especially during the transition off glipizide. 1

• Monitor renal function every 3-6 months if adding Synjardy XL. 1

• Temporarily discontinue SGLT2 inhibitors (empagliflozin component) during acute illness with vomiting, diarrhea, or volume depletion. 1

Common Pitfalls to Avoid

• Do not add Synjardy XL while continuing glipizide, as this creates excessive polypharmacy and hypoglycemia risk without addressing the fundamental issue of inadequate basal insulin dosing. 1

• Avoid using glyburide (mentioned as "glipiZIDE" but clarify if actually glyburide) in elderly patients, as it has the highest hypoglycemia risk among sulfonylureas and should generally not be prescribed to older adults. 1

• Do not pursue HbA1c <7.0% in this elderly patient, as intensive glycemic control increases mortality and hypoglycemia risk without clinical benefit in this population. 1

• Ensure adequate insulin titration before adding more oral agents, as premature addition of medications increases complexity, cost, and side effect burden without addressing inadequate basal coverage. 1