What are the risks and benefits of using Jardiance (empagliflozin) or Farxiga (dapagliflozin) in patients with type 2 diabetes?

SGLT2 Inhibitors for Type 2 Diabetes: Jardiance vs Farxiga

Both Jardiance (empagliflozin) and Farxiga (dapagliflozin) provide substantial cardiovascular and renal benefits beyond glucose control in patients with type 2 diabetes, with empagliflozin demonstrating superior mortality reduction (38% reduction in cardiovascular death) while dapagliflozin shows broader heart failure benefits across both reduced and preserved ejection fraction. 1, 2

Cardiovascular Benefits

Empagliflozin (Jardiance)

• Reduces cardiovascular death by 38% in patients with type 2 diabetes and established cardiovascular disease 1, 2
• Demonstrated significant reduction in 3-point MACE (major adverse cardiovascular events: nonfatal MI, nonfatal stroke, CV death) with p=0.04 for superiority vs placebo 1
• Reduces hospitalization for heart failure or cardiovascular death as a composite endpoint 1
• FDA-approved specifically to reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease 3

Dapagliflozin (Farxiga)

• Reduces heart failure hospitalization by 26-30% in patients with heart failure with reduced ejection fraction (HFrEF) 1, 2
• Provides 18% reduction in heart failure hospitalization in patients with heart failure with preserved ejection fraction (HFpEF) 2
• FDA-approved to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes and established cardiovascular disease or multiple cardiovascular risk factors 1
• Also approved to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with HFrEF 1

Renal Protection

Both Agents

• Both medications reduce progression of diabetic kidney disease 2
• Dapagliflozin specifically demonstrates 39% reduction in composite renal outcomes and 44% reduction in sustained eGFR decline ≥50%, end-stage kidney disease, or renal death 2
• Empagliflozin reduces risk of end-stage kidney disease, doubling of serum creatinine, cardiovascular death, and hospitalization for heart failure in patients with diabetic nephropathy with albuminuria 1

Glycemic Control

• Both agents provide moderate glucose-lowering with HbA1c reductions of approximately 0.5-0.8% 4, 5
• Efficacy increases with higher baseline hyperglycemia but decreases significantly in patients with renal impairment 4, 5
• Both carry low inherent risk of hypoglycemia due to insulin-independent mechanism of action 6, 7

Additional Metabolic Benefits

• Both agents reduce body weight by approximately 2 kg through calorie loss via glucosuria 6, 5, 8
• Both lower systolic blood pressure by approximately 4 mmHg and diastolic by approximately 2 mmHg through osmotic diuresis 5, 8
• These effects occur independently of glucose control 6

Dosing and Renal Considerations

Empagliflozin (Jardiance)

• Standard dose: 10 mg once daily 1
• Not recommended for glycemic control if eGFR <45 mL/min/1.73 m² 1
• Contraindicated in patients on dialysis or with severe renal impairment 1
• Can be continued for cardiovascular benefits even when eGFR falls below glycemic efficacy threshold 2

Dapagliflozin (Farxiga)

• Standard dose: 10 mg once daily 1
• Not recommended for glycemic control if eGFR <45 mL/min/1.73 m² 1
• Contraindicated if eGFR <30 mL/min/1.73 m² 1
• Should be continued for cardiorenal benefits even when eGFR falls below glycemic efficacy threshold 2

Critical Safety Concerns

Euglycemic Diabetic Ketoacidosis (DKA)

• Both agents carry risk of euglycemic DKA, which can occur with normal or only slightly elevated blood glucose levels (<200 mg/dL) 9, 10
• Discontinue at least 3-4 days before planned surgery to prevent postoperative ketoacidosis 1, 9
• Stop immediately if symptoms of ketoacidosis develop (nausea, vomiting, abdominal pain, tiredness, trouble breathing) 9, 10

High-Risk Situations for DKA

• Reduced caloric intake, prolonged fasting, or illness 9
• Acute infection or metabolic stress 9
• Surgical procedures 9
• Alcohol consumption 9
• Volume depletion 9
• Patients with insulin deficiency 9

Genital and Urinary Infections

• Genital mycotic infections are the most common adverse event, particularly in women 1, 7, 8
• Mild increase in urinary tract infections, though generally negligible 5, 8
• Use with caution in patients at risk for recurrent urinary tract infections 8

Volume Depletion and Hypotension

• Both agents can cause volume depletion through osmotic diuresis 1, 5
• Higher risk in elderly patients, those on diuretics, or patients with low baseline systolic blood pressure 9
• Consider stopping or reducing diuretic dose when initiating therapy 1
• Assess volume status carefully before initiation in elderly patients 2

Amputation and Fracture Risk

• Empagliflozin has NOT been associated with increased risk of amputation or bone fractures, unlike canagliflozin 6
• Dapagliflozin has not shown increased fracture risk in clinical trials 7

Contraindications

Both Agents

• History of serious hypersensitivity reaction to the drug 1
• Severe renal impairment or end-stage renal disease 1
• Not recommended for type 1 diabetes or treatment of diabetic ketoacidosis 10, 3

Dapagliflozin-Specific

• Pregnancy or breastfeeding 1

Clinical Decision Algorithm

Choose Empagliflozin (Jardiance) When:

• Primary goal is cardiovascular mortality reduction in patients with established cardiovascular disease 1, 2
• Patient has type 2 diabetes with history of myocardial infarction or stroke 1
• Concern about amputation risk (empagliflozin has no increased risk) 6

Choose Dapagliflozin (Farxiga) When:

• Primary goal is heart failure hospitalization reduction, especially in patients with HFrEF or HFpEF 1, 2
• Patient has type 2 diabetes with heart failure (any ejection fraction) 2
• Broader heart failure indication is needed beyond just cardiovascular disease 1

Prioritize Either Agent When:

• Patient has diabetic kidney disease with albuminuria (both provide renal protection) 1, 2
• Patient needs weight loss and blood pressure reduction in addition to glucose control 6, 5, 8
• Patient is at high cardiovascular risk and requires cardioprotection 2, 6

Common Pitfalls to Avoid

• Never continue SGLT2 inhibitors through surgical procedures—stop 3-4 days before surgery 1, 9
• Do not rely solely on blood glucose monitoring to detect DKA; check ketones if symptoms present 9, 10
• Avoid initiating in patients with active genital or urinary infections 8
• Do not use in patients with recurrent DKA history 10
• Reassess need for concomitant diuretics or antihypertensives to prevent excessive volume depletion 1
• Educate patients about DKA symptoms and when to seek immediate care 9, 10
• Monitor renal function regularly, but continue for cardiovascular benefits even when glycemic efficacy diminishes 2