Empagliflozin (Jardiance®)

Dr. Akhila Gandikota
2 days ago
4 min read

Updated: 22 hours ago

Drug class: SGLT2 inhibitor

Mechanism of Action

Empagliflozin inhibits the SGLT2 found in proximal tubules in the kidneys. It reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion (1).

It also reduces sodium reabsorption, thereby enhancing tubuloglomerular feedback, lowering intraglomerular pressure, reducing cardiac pre- and afterload, and downregulating sympathetic activity (1).

Approved Indications

Type 2 diabetes mellitus (1)
Heart failure with reduced ejection fraction (HFrEF) (1)
Chronic kidney disease (CKD) (1)

Dosage and Administration

10 mg once daily (may increase to 25 mg once daily) (1)

Key clinical benefits

Improves glycemic control (1)
Reduces CV mortality in HFrEF (1)
Slows CKD progression (1)

Key clinical trials

EMPA-REG OUTCOME

In a randomized trial involving 7,020 patients with type 2 diabetes at high cardiovascular risk, empagliflozin was evaluated against placebo on top of standard care. The primary endpoint, a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, occurred in 10.5% of patients receiving empagliflozin compared with 12.1% in the placebo group (HR 0.86; 95.02% CI 0.74–0.99; P=0.04).

Empagliflozin significantly reduced cardiovascular death (3.7% vs. 5.9%; 38% relative risk reduction), hospitalization for heart failure (2.7% vs. 4.1%; 35% RRR), and all‑cause mortality (5.7% vs. 8.3%; 32% RRR). However, there was no significant difference in rates of myocardial infarction, stroke, or the key secondary composite outcome that included hospitalization for unstable angina (P=0.08) (2).

EMPEROR-Reduced

EMPEROR-Reduced and EMPEROR-Preserved are two landmark trials that evaluated empagliflozin in chronic heart failure (3,4). In the EMPEROR-Reduced trial, 3,730 patients with symptomatic HFrEF were randomized to receive empagliflozin 10 mg once daily or placebo in addition to guideline-directed therapy. Empagliflozin significantly reduced the risk of the primary composite endpoint of cardiovascular death or hospitalization for heart failure compared with placebo (19.4% vs. 24.7%; HR 0.75; 95% CI 0.65–0.86; P<0.001). The benefit was primarily driven by a reduction in heart failure hospitalizations, with empagliflozin also slowing the decline in renal function. The treatment effect was consistent regardless of the presence or absence of T2DM (3).

EMPEROR-Preserved

In the EMPEROR-Preserved trial, 5,988 patients with symptomatic heart failure and a left ventricular ejection fraction >40% were randomized to receive empagliflozin 10 mg once daily or placebo in addition to standard therapy. Empagliflozin significantly reduced the risk of the primary composite outcome of cardiovascular death or hospitalization for heart failure compared with placebo (13.8% vs. 17.1%; HR 0.79; 95% CI 0.69–0.90; P<0.001). The treatment benefit was mainly due to reduction in heart failure hospitalizations, while the effect on cardiovascular mortality was not significant. Genital and urinary tract infections, as well as hypotension, occurred more frequently in patients receiving empagliflozin (4).

EMPA-KIDNEY

In the EMPA-KIDNEY trial, 6,609 patients with chronic kidney disease, with or without diabetes, were randomized to receive empagliflozin 10 mg once daily or placebo in addition to standard care. Over a median follow-up of 2.0 years, empagliflozin significantly reduced the risk of the primary composite outcome of kidney disease progression or death from cardiovascular causes compared with placebo (13.1% vs. 16.9%; HR 0.72; 95% CI 0.64–0.82; P<0.001). The treatment benefit was consistent among patients with and without diabetes and across eGFR subgroups. Empagliflozin was also associated with a lower rate of hospitalization from any cause compared with placebo (HR 0.86; 95% CI 0.78–0.95; P=0.003). However, no significant between-group differences were observed in the composite outcome of hospitalization for heart failure or cardiovascular death, or in all-cause mortality. The rates of serious adverse events were similar between the empagliflozin and placebo groups (5).

Common Adverse Events

Genital infections (1)
Urinary tract infections (1)
Increased urination (1)
Hypotension/dizziness (volume depletion) (1)

Contraindications/Precautions

Severe renal impairment (eGFR <30 mL/min/1.73m²) (1)
History of ketoacidosis (1)
Genitourinary infections (1)
Use with caution in elderly or dehydrated patients (1)

Special notes for the clinician

Not recommended in type 1 diabetes
Educate patients on hydration and infection risk

Abbreviations

CI: confidence interval; CKD: chronic kidney disease; DM: diabetes mellitus; eGFR: estimated glomerular filtration rate; HFrEF: heart failure with reduced ejection fraction; HR: hazard ratio; SGLT2: sodium-glucose cotransporter 2.

References

Boehringer Ingelheim Pharmaceuticals, Inc. JARDIANCE® (empagliflozin tablets): US prescribing information. Ridgefield (CT): Boehringer Ingelheim Pharmaceuticals, Inc.; 2025. Available from: Jardiance US Prescribing Information
Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-28. doi:10.1056/NEJMoa1504720.
Wagdy K, Nagy S. EMPEROR-Preserved: SGLT2 inhibitors breakthrough in the management of heart failure with preserved ejection fraction. Glob Cardiol Sci Pract. 2021;2021:17. doi:10.21542/gcsp.2021.17.
Wagdy K. The EMPEROR-Reduced trial: SGLT2 inhibitors for heart failure get more support. Glob Cardiol Sci Pract. 2020;2020(3):e202031. doi:10.21542/gcsp.2020.31.
Herrington WG, Staplin N, Wanner C, et al.; EMPA-KIDNEY Collaborative Group. Empagliflozin in patients with chronic kidney disease. N Engl J Med. 2023;388(2):117-127. doi:10.1056/NEJMoa2204233.

About the Author

Dr. Akhila Gandikota (PharmD) is a Scientific Writer with over five years of experience in medical communications and clinical research. She specializes in creating evidence‑based scientific content, including publications, training materials, and medical education resources. Passionate about translating complex research into clear, impactful communication, Dr. Akhila combines her clinical expertise with a strong foundation in scientific writing, ensuring accuracy, accessibility, and meaningful engagement across diverse audiences.

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