What medications can be added to Jardiance (Empagliflozin) for improved glycemic control?

Medications to Add to Jardiance (Empagliflozin)

Add metformin as the first-line medication to Jardiance if the patient is not already taking it, as this combination provides complementary mechanisms of action with established efficacy and safety. 1

Primary Addition: Metformin

• Metformin should be added to Jardiance for most patients not already taking it, as it works by increasing insulin sensitivity while Jardiance works through an insulin-independent mechanism, creating a synergistic effect for glycemic control 1
• This combination typically lowers HbA1c by approximately 0.7-1.0% beyond what either agent achieves alone 1
• Metformin is safe to use with Jardiance if eGFR is >30 mL/min/1.73 m² 1

For Patients with Cardiovascular Disease or High CV Risk

If the patient has established atherosclerotic cardiovascular disease (ASCVD), heart failure, or chronic kidney disease, add a GLP-1 receptor agonist with proven cardiovascular benefit (liraglutide, semaglutide, or dulaglutide) to the Jardiance regimen. 1

• GLP-1 receptor agonists (liraglutide, semaglutide, or dulaglutide) are recommended to reduce cardiovascular events and mortality in patients with T2D and CVD 1
• The combination of an SGLT2 inhibitor (Jardiance) and GLP-1 RA provides dual cardioprotective benefits through different mechanisms 1
• This combination addresses both heart failure risk (via Jardiance) and MACE reduction (via GLP-1 RA) 1
• Do NOT combine GLP-1 receptor agonists with DPP-4 inhibitors, as there is no added glucose-lowering benefit beyond the GLP-1 RA alone 1

For Patients Requiring Additional Glycemic Control

If HbA1c is 1.5-2.0% Above Goal:

• Add a GLP-1 receptor agonist (liraglutide, semaglutide, or dulaglutide) as these provide 1-2% HbA1c reduction with weight loss benefits and low hypoglycemia risk 1
• Consider fixed-ratio combination products (IDegLira or iGlarLixi) if both GLP-1 RA and basal insulin are needed 1

If HbA1c is >2.0% Above Goal or >10%:

• Initiate basal insulin (NPH or long-acting analog) in addition to Jardiance, particularly if symptoms of hyperglycemia or ongoing catabolism are present 1
• However, if not already on a GLP-1 RA, start this first as it may be sufficient with lower hypoglycemia risk 1

Alternative Add-On Options

DPP-4 Inhibitors (if GLP-1 RA not feasible):

• Consider sitagliptin or linagliptin for patients who cannot tolerate or afford GLP-1 receptor agonists 1, 2, 3
• These provide moderate HbA1c reduction (0.4-0.9%) with minimal hypoglycemia risk 3
• Avoid saxagliptin in patients with heart failure risk, as it increases heart failure hospitalization 1, 3
• Linagliptin requires no dose adjustment in renal impairment, making it preferable for CKD patients if a DPP-4 inhibitor is chosen 3

Sulfonylureas or Insulin:

• Add sulfonylureas (e.g., gliclazide) or insulin only if the above options are contraindicated or insufficient 1
• Be aware these increase hypoglycemia and weight gain risk 1

Important Clinical Considerations

Avoid Therapeutic Inertia:

• Treatment intensification should not be delayed when patients are not meeting individualized glycemic goals 1
• Reassess therapy every 3-6 months if targets are not achieved 1

Common Pitfalls:

• Never combine GLP-1 receptor agonists with DPP-4 inhibitors—no additional benefit and increased cost 1
• Avoid thiazolidinediones (pioglitazone, rosiglitazone) in patients with heart failure 1
• Monitor for volume depletion when combining Jardiance with other diuretics or antihypertensive drugs 4
• Watch for genital infections (3.7-5.6% incidence) and urinary tract infections (5.1-5.6% incidence) with Jardiance combinations 5

Renal Function Monitoring:

• SGLT2 inhibitors like Jardiance can be initiated if eGFR is above 20 mL/min/1.73 m² 1
• Metformin should be used cautiously if eGFR <45 mL/min/1.73 m² and avoided if <30 mL/min/1.73 m² 1

Treatment Algorithm Summary

1. First priority: Add metformin if not already prescribed 1
2. If CVD/HF/CKD present: Add GLP-1 RA with proven CV benefit (liraglutide, semaglutide, or dulaglutide) 1
3. If HbA1c 1.5-2.0% above goal: Add GLP-1 RA for potent glucose lowering with weight benefits 1
4. If HbA1c >2.0% above goal or >10%: Consider GLP-1 RA first, then basal insulin if needed 1
5. If GLP-1 RA not feasible: Consider DPP-4 inhibitor (linagliptin or sitagliptin, NOT saxagliptin) 2, 3
6. Last resort: Add sulfonylurea or intensify insulin therapy 1