When to start Jardiance (Empagliflozin) in a patient with type 2 diabetes mellitus (T2DM) and inadequate glycemic control or a history of cardiovascular disease (CVD)?

When to Start Jardiance (Empagliflozin) in Type 2 Diabetes

Start Jardiance immediately in any patient with type 2 diabetes who has established cardiovascular disease (prior MI, stroke, revascularization) or chronic kidney disease (eGFR 20-60 mL/min/1.73 m² or albuminuria ≥30 mg/g), regardless of their current HbA1c level, metformin use, or whether they are at glycemic goal. 1

Primary Indications for Immediate Initiation

Patients with Established Cardiovascular Disease

• Jardiance should be started in all patients with type 2 diabetes and any history of atherosclerotic cardiovascular disease, including prior myocardial infarction, ischemic stroke, unstable angina, or coronary/carotid/peripheral artery revascularization. 1
• The cardiovascular benefits are independent of glucose-lowering effects and do not require baseline metformin therapy. 1
• Empagliflozin reduces cardiovascular death by 38% and all-cause mortality by 32% in this population. 2

Patients with Chronic Kidney Disease

• Initiate Jardiance in patients with eGFR ≥20 mL/min/1.73 m² and continue it even as eGFR declines below this threshold once started. 1
• Start immediately if albuminuria is present (ACR ≥30 mg/g), particularly if ACR >300 mg/g. 1
• Empagliflozin reduces progression to macroalbuminuria by 38%, doubling of creatinine by 44%, and need for renal replacement therapy by 55%. 2

Patients with Heart Failure

• Begin Jardiance in any patient with type 2 diabetes and heart failure, particularly those with reduced ejection fraction (<45%). 1
• Empagliflozin reduces heart failure hospitalization by 35% across the spectrum of cardiovascular disease and heart failure risk. 2
• This benefit appears rapidly (within months) and is likely related to the diuretic effect rather than glucose lowering. 3, 2

Secondary Indications Based on Risk Profile

High Cardiovascular Risk Without Established Disease

• Consider starting Jardiance in patients aged ≥55 years with indicators of high cardiovascular risk, including: 1
  • Coronary, carotid, or lower extremity artery stenosis >50%
  • Left ventricular hypertrophy
  • eGFR <60 mL/min/1.73 m²
  • Albuminuria (even if <300 mg/g)

Inadequate Glycemic Control

• Start Jardiance when HbA1c remains >7% despite metformin monotherapy, as it provides an additional 0.5-0.8% HbA1c reduction. 4
• The glucose-lowering effect is moderate but consistent across baseline HbA1c levels of 7-10%. 4
• In patients with renal impairment, the glucose-lowering effect is diminished, but cardiovascular and renal benefits persist. 3, 2

Critical Implementation Details

Dosing Strategy

• Begin with empagliflozin 10 mg once daily, with consideration for increasing to 25 mg if additional glucose lowering is needed and the medication is well tolerated. 5, 4
• Both doses provide similar cardiovascular and renal benefits; the 25 mg dose offers slightly greater HbA1c reduction (0.8% vs 0.7%). 4

Independence from Other Therapies

• Do not wait to optimize metformin or achieve specific HbA1c targets before starting Jardiance in high-risk patients. 1
• The drug can be initiated independent of baseline A1C or individualized A1C goal. 1
• If the patient is already on dual therapy or multiple glucose-lowering agents without an SGLT2 inhibitor, consider switching one agent to empagliflozin. 1

Renal Function Considerations

• Jardiance can be initiated down to eGFR 20 mL/min/1.73 m² and continued below this threshold once started. 1
• Metformin should be reduced to 1000 mg daily when eGFR is 30-44 mL/min/1.73 m², but this does not affect the decision to use empagliflozin. 1

Important Safety Considerations and Monitoring

Contraindications and Cautions

• Avoid in patients with active foot ulcers or high amputation risk until careful shared decision-making occurs with comprehensive foot care education. 1
• Monitor for volume depletion, particularly in patients on other diuretics or antihypertensive medications, as empagliflozin has diuretic effects. 3, 2
• Be vigilant for genital infections, diabetic ketoacidosis (even with normal glucose), and acute kidney injury. 1, 3

Blood Pressure Effects

• Empagliflozin reduces systolic blood pressure by 2.6-3.4 mmHg, which contributes to cardiovascular benefits but may require adjustment of other antihypertensives. 4, 2

Hypoglycemia Risk

• Jardiance carries a low inherent risk of hypoglycemia due to its insulin-independent mechanism, making it safe for use without aggressive dose titration of other agents. 6
• When combined with insulin or sulfonylureas, consider reducing doses of these agents to prevent hypoglycemia. 1

Common Clinical Pitfalls to Avoid

• Do not delay initiation waiting for "optimal" metformin dosing or HbA1c levels in patients with established CVD or CKD—the mortality benefit is independent of glucose lowering. 1
• Do not withhold empagliflozin solely based on eGFR if it is ≥20 mL/min/1.73 m²—renal benefits persist even with reduced glucose-lowering efficacy. 1, 2
• Do not prioritize thiazolidinediones or saxagliptin over SGLT2 inhibitors in patients with cardiovascular disease or heart failure, as these agents increase heart failure risk. 5
• Do not assume all SGLT2 inhibitors are equivalent—empagliflozin specifically has not been associated with increased amputation risk (unlike canagliflozin). 6