Is empagliflozin (Jardiance) appropriate for an adult with type 2 diabetes who needs additional glucose lowering beyond diet, exercise and metformin?

Is Jardiance (Empagliflozin) a Good Medication for Diabetics?

Yes, Jardiance is an excellent medication for adults with type 2 diabetes, particularly when added to metformin after lifestyle modifications prove insufficient, and it should be strongly prioritized in patients with established cardiovascular disease, heart failure, or chronic kidney disease because it reduces cardiovascular death, heart failure hospitalization, and kidney disease progression. 1

When to Use Jardiance

First-Line Therapy Considerations

• Metformin remains the mandatory first-line medication for most adults with type 2 diabetes, combined with lifestyle modifications. 1, 2
• Jardiance should be added as second-line therapy when metformin plus lifestyle changes fail to achieve glycemic control after approximately 3 months. 1, 2
• In patients with established cardiovascular disease, heart failure, or chronic kidney disease at diagnosis, Jardiance may be started immediately alongside metformin, independent of baseline HbA1c, because cardiovascular and renal benefits outweigh waiting for metformin "failure." 1, 2

Prioritize Jardiance Over Other Options When:

• The patient has congestive heart failure – Jardiance reduces heart failure hospitalization by 35% with high-certainty evidence. 1, 2
• The patient has chronic kidney disease (eGFR ≥30 mL/min/1.73 m²) – Jardiance slows CKD progression and reduces end-stage kidney disease risk by 30-32%. 1, 2
• The patient has established atherosclerotic cardiovascular disease – Jardiance reduces cardiovascular death by 38% and all-cause mortality by 32%. 1
• Cardiovascular mortality reduction is the priority – Jardiance is the only SGLT2 inhibitor specifically FDA-approved to reduce cardiovascular death in adults with type 2 diabetes and established cardiovascular disease. 1, 3

Choose a GLP-1 Agonist Instead When:

• The patient has increased stroke risk as the dominant concern – GLP-1 agonists reduce stroke more effectively than SGLT2 inhibitors. 2, 4
• Weight loss is the primary treatment goal – GLP-1 agonists produce greater weight reduction (5-15 kg) compared to Jardiance (2-4 kg). 2, 4

Dosing and Administration

• Start Jardiance 10 mg once daily in the morning, with or without food. 3
• Increase to 25 mg once daily in patients tolerating the 10 mg dose if HbA1c remains above target (7-8%). 3
• Jardiance can be initiated when eGFR is ≥45 mL/min/1.73 m² for full glucose-lowering efficacy. 3
• Between eGFR 30-44 mL/min/1.73 m², glucose-lowering effect diminishes but cardiovascular and renal benefits persist, so initiation is still recommended. 1, 2
• Discontinue Jardiance if eGFR falls persistently below 45 mL/min/1.73 m² or if the patient requires dialysis. 1, 3

Safety Profile and Monitoring

Low Hypoglycemia Risk

• Jardiance combined with metformin carries minimal hypoglycemia risk because both work through insulin-independent mechanisms. 1, 2
• When adding Jardiance to a regimen containing sulfonylureas or long-acting insulin, immediately reduce or discontinue those medications to prevent severe hypoglycemia. 1, 2
• Self-monitoring of blood glucose is likely unnecessary when Jardiance is combined only with metformin. 2

Volume Depletion and Hypotension

• Jardiance causes osmotic diuresis and intravascular volume contraction, which may lead to symptomatic hypotension, particularly in elderly patients, those with low baseline blood pressure, or those taking diuretics. 1, 3
• Assess volume status before initiating Jardiance and correct any volume depletion. 3
• Use caution when combining Jardiance with loop diuretics, ACE inhibitors, or ARBs, and monitor for orthostatic hypotension. 2

Ketoacidosis Risk

• Euglycemic diabetic ketoacidosis is a rare but serious adverse effect reported with all SGLT2 inhibitors, including Jardiance. 1, 3
• Discontinue Jardiance at least 3 days before planned surgery to prevent postoperative ketoacidosis. 1
• Educate patients to stop Jardiance and seek immediate medical care if they develop nausea, vomiting, dyspnea, or unusual fatigue. 2

Genital and Urinary Infections

• Genital fungal infections occur more frequently with Jardiance, especially in women, due to increased urinary glucose excretion. 1, 5
• Urinary tract infections show a negligible increase in incidence. 1

Renal Function Monitoring

• Measure eGFR at baseline, 2 weeks after starting Jardiance, then every 3-6 months. 2
• Continue metformin at the current dose when adding Jardiance unless eGFR falls below 30 mL/min/1.73 m². 1, 2

Cardiovascular and Renal Benefits Beyond Glucose Control

• In the EMPA-REG OUTCOME trial, Jardiance reduced the primary composite endpoint of cardiovascular death, myocardial infarction, or stroke by 14% (HR 0.86,95% CI 0.74-0.99). 1
• The 38% reduction in cardiovascular death (HR 0.62,95% CI 0.49-0.77) and 32% reduction in all-cause mortality (HR 0.68,95% CI 0.57-0.82) were driven predominantly by cardiovascular death reduction. 1
• Heart failure hospitalization was reduced by 35% (HR 0.65,95% CI 0.50-0.85), with benefit evident within weeks of initiation. 1
• These cardiovascular and renal benefits occur largely independent of glycemic control, meaning Jardiance provides protection even in patients already at HbA1c goal. 1, 5

Glycemic Efficacy

• Jardiance monotherapy or add-on therapy reduces HbA1c by approximately 0.8% compared to placebo. 1, 5, 6
• This glucose-lowering effect is similar to metformin, glimepiride, and sitagliptin but with the advantage of weight reduction and blood pressure lowering. 6, 7
• Jardiance produces modest weight loss of approximately 2-4 kg through urinary glucose excretion (approximately 70 g glucose/day or 200-300 kcal/day). 2, 8, 7
• Jardiance reduces systolic blood pressure by approximately 4 mmHg and diastolic blood pressure by approximately 2 mmHg. 6, 7

What NOT to Do

• Do not add a DPP-4 inhibitor to a regimen containing Jardiance – DPP-4 inhibitors provide no mortality or morbidity benefit and offer no additional glucose lowering beyond Jardiance alone. 1, 2
• Do not continue full-dose sulfonylureas when Jardiance achieves adequate glycemic control – this creates severe hypoglycemia risk that negates the mortality benefits of SGLT2 inhibitor therapy. 1, 2
• Do not delay Jardiance initiation in patients with heart failure or CKD while awaiting metformin "failure" – both agents should be started early in high-risk patients. 1, 2

Cost Considerations

• No generic empagliflozin currently exists, so Jardiance costs several hundred dollars per month without insurance coverage. 2
• Discuss medication costs with patients when selecting therapy, but prioritize mortality reduction over cost when feasible. 2, 4
• Explore patient assistance programs if cost is prohibitive. 4

Special Populations

Pediatric Use

• Empagliflozin is now approved for use in youth aged 10-17 years with type 2 diabetes. 1
• In a multicenter trial of 158 children, empagliflozin (pooled 10 mg and 25 mg groups) reduced HbA1c by 0.84% compared to placebo (P = 0.012) with no episodes of severe hypoglycemia. 1

Contraindications

• History of serious hypersensitivity reaction to empagliflozin. 3
• Severe renal impairment (eGFR <30 mL/min/1.73 m²), end-stage renal disease, or dialysis. 3

Comparison to Other SGLT2 Inhibitors

• Unlike canagliflozin, Jardiance has not been associated with increased risk of amputation or bone fractures. 5
• Jardiance is the only SGLT2 inhibitor specifically FDA-approved to reduce cardiovascular death in adults with type 2 diabetes and established cardiovascular disease. 1, 3
• All SGLT2 inhibitors (empagliflozin, canagliflozin, dapagliflozin) demonstrate similar cardiovascular and renal benefits, but empagliflozin has the most robust mortality data. 1, 2