Can Jardiance (empagliflozin) be added to Metformin ER (extended release) 500 mg and Glyburide (glypezide) for inadequate glycemic control?

Adding Jardiance to Metformin ER and Glypezide for Diabetes Management

Yes, Jardiance (empagliflozin) can and should be added to Metformin ER 500 mg and glipizide for improved glycemic control and cardiovascular/renal protection in patients with type 2 diabetes. 1

Rationale for Adding Jardiance

The American College of Physicians (ACP) strongly recommends adding an SGLT2 inhibitor like Jardiance to metformin in patients with inadequate glycemic control, based on high-certainty evidence 1. This recommendation is particularly important because:

• SGLT2 inhibitors reduce the risk of all-cause mortality, major adverse cardiovascular events, chronic kidney disease progression, and hospitalization for heart failure 1
• Jardiance has demonstrated efficacy when added to metformin and sulfonylurea therapy in clinical trials 2
• The combination provides complementary mechanisms of action:
  • Metformin: Decreases hepatic glucose production
  • Glipizide (sulfonylurea): Increases insulin secretion
  • Jardiance: Increases urinary glucose excretion (insulin-independent mechanism)

Efficacy of Triple Therapy

When added to metformin and sulfonylurea therapy, Jardiance provides:

• Statistically significant reductions in HbA1c (-0.6% compared to placebo) 2
• Significant reductions in fasting plasma glucose (-29 mg/dL compared to placebo) 2
• Weight reduction (-2.9% with Jardiance 10mg vs -0.5% with placebo) 2

Important Safety Considerations

Hypoglycemia Risk

• When adding Jardiance to this combination, consider reducing the sulfonylurea (glipizide) dose to minimize hypoglycemia risk 1
• The ACP specifically notes: "When adding an SGLT2 inhibitor results in adequate glycemic control, clinicians should reduce or discontinue existing treatment with sulfonylureas due to increased risk for severe hypoglycemia" 1

Other Safety Considerations

• Monitor for genital mycotic infections (most common side effect) 1, 3
• Advise patient about the rare risk of euglycemic diabetic ketoacidosis 1, 3
• Ensure adequate renal function (eGFR ≥30 mL/min/1.73 m²) before initiating 3
• Jardiance is well-tolerated with metformin with no significant drug-drug interactions 4

Dosing Recommendations

• Start with Jardiance 10 mg once daily 3
• Can be increased to 25 mg daily if needed and tolerated 2
• No dose adjustment needed for Metformin ER 500 mg when adding Jardiance 4
• Consider reducing glipizide dose if hypoglycemia occurs 1

Cardiovascular and Renal Benefits

Beyond glycemic control, this combination offers additional benefits:

• Jardiance reduces cardiovascular mortality and hospitalization for heart failure 3
• Provides renal protection by slowing progression of chronic kidney disease 1
• These benefits occur regardless of baseline HbA1c 1

Monitoring Recommendations

• Regular monitoring of renal function
• Watch for symptoms of genital infections or urinary tract infections
• Monitor for hypoglycemia, especially during initial titration period
• No need for increased self-monitoring of blood glucose with this combination 1

This triple therapy approach aligns with current guidelines that prioritize medications offering cardiovascular and renal protection while providing effective glycemic control with minimal hypoglycemia risk.