Is it safe to give glipizide and Synjardy (empagliflozin/metformin) together?

Combining Glipizide and Synjardy (Empagliflozin/Metformin) in Diabetes Management

Yes, glipizide and Synjardy (empagliflozin/metformin) can be safely used together, but dose adjustments and careful monitoring are necessary to avoid hypoglycemia. 1

Pharmacological Considerations

• Glipizide is a second-generation sulfonylurea that stimulates insulin secretion from pancreatic beta cells 1
• Synjardy combines empagliflozin (an SGLT2 inhibitor) and metformin (a biguanide) with complementary mechanisms of action 2
• The combination provides multiple mechanisms to control blood glucose:
  • Glipizide increases insulin secretion 1
  • Empagliflozin promotes urinary glucose excretion 1
  • Metformin decreases hepatic glucose production and improves insulin sensitivity 1

Safety Considerations

Hypoglycemia Risk

• When adding Synjardy to glipizide therapy, there is an increased risk of hypoglycemia that requires careful management 1
• Consider reducing the glipizide dose by 50% when initiating Synjardy to minimize hypoglycemia risk 1
• Monitor blood glucose levels closely, especially during the initial titration period 1

Renal Function Considerations

• Metformin component of Synjardy should not be used in patients with:
  • eGFR <30 mL/min/1.73m² 1
  • Serum creatinine ≥1.5 mg/dL in men or ≥1.4 mg/dL in women 1
• Empagliflozin efficacy is dependent on renal function; reduced glucose-lowering effect is seen with declining kidney function 1
• Glipizide is preferred over other sulfonylureas in renal impairment as it does not have active metabolites 1

Monitoring Recommendations

• Monitor renal function:
  • At least annually if eGFR ≥60 mL/min/1.73m² 1
  • Every 3-6 months if eGFR 30-59 mL/min/1.73m² 1
• Assess for signs and symptoms of hypoglycemia, especially during initial combination therapy 1
• Monitor for potential side effects:
  • Genital mycotic infections (from empagliflozin) 1
  • Gastrointestinal side effects (from metformin) 2
  • Risk of euglycemic diabetic ketoacidosis (from empagliflozin) 1

Clinical Evidence

• Studies have demonstrated that combining a sulfonylurea with metformin and an SGLT2 inhibitor can provide better glycemic control than dual therapy alone 3
• A study evaluating empagliflozin add-on therapy to metformin and glimepiride (another sulfonylurea) showed:
  • Significant decrease in HbA1c (16.1% reduction)
  • Better fasting blood sugar control (23.8% decrease)
  • Modest weight reduction (1.5% decrease in BMI) 3
• The combination of glipizide and metformin has been shown to be more effective than either agent alone in controlling HbA1c 4

Practical Recommendations

• Start with standard doses of glipizide and consider reducing the dose when adding Synjardy 1
• Initiate Synjardy at a low dose and titrate gradually to minimize gastrointestinal side effects 2
• Educate patients about:
  • Signs and symptoms of hypoglycemia 1
  • Need for regular blood glucose monitoring 1
  • Potential for genital mycotic infections with SGLT2 inhibitor component 1
• Temporarily withhold Synjardy during periods of:
  • Severe illness
  • Dehydration
  • Surgery
  • Reduced oral intake 1

Special Populations

• In patients with established cardiovascular disease or heart failure, the empagliflozin component of Synjardy offers cardiovascular benefits 1
• In patients with chronic kidney disease, glipizide is preferred over other sulfonylureas, but dose adjustments may be needed 1
• In elderly patients, start with lower doses of both medications and monitor more frequently for hypoglycemia 1

By following these recommendations, the combination of glipizide and Synjardy can be used safely and effectively to manage type 2 diabetes while minimizing risks of adverse events.