Jardiance (empagliflozin) - 4 indications

Scroll down for information on each indication:

• for the treatment of type II diabetes; approved August 2014
• to reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and cardiovascular disease; approved December 2016
• to reduce the risk of cardiovascular death plus hospitalization for heart failure in adults with heart failure with reduced ejection fraction; approved August 2021; expanded in February of 2022 to include all heart failure patients
• to reduce the risk of sustained decline in eGFR, end-stage kidney disease, cardiovascular death, and hospitalization in adults with chronic kidney disease at risk of progression; approved September 2023

General Information

Jardiance (empagliflozin) is a sodium-glucose co-transporter 2 (SGLT2) inhibitor.

Jardiance is specifically indicated for the following:

• as an adjunct to diet and exercise to improve glycemic control in patients >10 of age with type II diabetes mellitus
• to reduce the risk of cardiovascular death in adults with type 2 diabetes mellitus and established cardiovascular disease
• to reduce the risk of cardiovascular death plus hospitalization for heart failure in adults with heart failure 
• to reduce the risk of sustained decline in eGFR, end-stage kidney disease, cardiovascular death, and hospitalization in adults with chronic kidney disease at risk of progression

Jardiance is supplied as a tablet for oral administration. The recommended dose is 10 mg once daily in the morning, taken with or without food. In patients tolerating Jardiance, the dose may be increased to 25 mg.

Mechanism of Action

Jardiance (empagliflozin) is a sodium-glucose co-transporter 2 (SGLT2) inhibitor. SGLT2 is the predominant transporter responsible for reabsorption of glucose from the glomerular filtrate back into the circulation. By inhibiting SGLT2, empagliflozin reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion. 

Side Effects

Adverse effects associated with the use of Jardiance may include, but are not limited to, the following:

• urinary tract infections
• female genital mycotic infections

Indication 1- as an adjunct to diet and exercise to improve glycemic control in patients >10 years of age with type II diabetes

approved August 2014; expanded age approved June 2023

Clinical Trial Results

The FDA approval of Jardiance was based on a monotherapy study and in combination study with metformin, sulfonylurea, pioglitazone and insulin. 

Monotherapy Study

A double-blind, placebo-controlled study enrolled 986 treatment-naïve subjects with inadequately controlled type II diabetes. The subjects entered an open-label placebo run-in for two weeks. At the end of the run-in period, subjects who remained inadequately controlled and had an HbA1c between 7 and 10% were randomized to placebo, Jardiance 10 mg, Jardiance 25 mg, or a reference comparator. At Week 24, treatment with Jardiance 10 mg or 25 mg daily provided statistically significant reductions in HbA1c (p-value <0.0001), fasting plasma glucose (FPG), and body weight compared with placebo. At Week 24, systolic blood pressure was statistically significantly reduced compared to placebo by -2.6 mmHg (placebo-adjusted, p-value=0.0231) in subjects randomized to 10 mg of Jardiance and by -3.4 mmHg (placebo-corrected, p-value=0.0028) in subjects randomized to 25 mg of Jardiance.

Combination Studies

In various combination studies, treatment with Jardiance 10 mg or 25 mg daily provided statistically significant reductions in HbA1c (p-value <0.0001), FPG, and body weight compared with placebo. 

Pediatrics

A double-blind, randomized, placebo-controlled trial enrolled 157 patients aged 10 to 17 years with inadequately controlled type 2 diabetes. Participants were randomly assigned to one of three treatment arms for 26 weeks: empagliflozin, a DPP-4 inhibitor (linagliptin), or placebo. At the beginning of the trial, 51% of patients were taking metformin alone, 40% of patients were taking a combination of metformin and insulin, 3% of patients were taking insulin alone, and 6% of patients were not taking other medicines for diabetes. The trial found that, at week 26, treatment with empagliflozin was superior in reducing hemoglobin A1c, a measure of average blood sugar, compared to placebo. The 52 patients treated with empagliflozin had an average 0.2% decrease in hemoglobin A1c compared with an average 0.7% increase in hemoglobin A1c in the 53 patients taking placebo, representing a 0.8% decrease in hemoglobin A1c with empagliflozin as compared to placebo. Patients treated with empagliflozin also had reductions in fasting plasma glucose, a blood sugar measurement taken after not eating or drinking for at least eight hours, as compared to patients taking placebo. 

Indication 2 - to reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and cardiovascular disease

approved December 2016

Clinical Trial Results

The FDA approval was based on a post-marketing study required by the agency when it approved Jardiance in 2014 as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Jardiance was studied in a post-market clinical trial of more than 7,000 patients with type 2 diabetes and cardiovascular disease. In the trial, Jardiance was shown to reduce the risk of cardiovascular death compared to a placebo when added to standard of care therapies for diabetes and atherosclerotic cardiovascular disease.

Indication 3 - to reduce the risk of cardiovascular death plus hospitalization for heart failure in adults with heart failure 

approved August 2021; expanded February of 2022

Clinical Trial Results

FDA approval was based on results from the EMPEROR-Reduced phase III trial, which investigated the effect of adding Jardiance 10 mg versus placebo to standard of care in a broad range of 3,730 adults with and without type 2 diabetes who had heart failure (functional class II, III or IV) and a left ventricular ejection fraction of 40% or less. In the trial, Jardiance significantly reduced the relative risk of the primary composite endpoint of time to cardiovascular death or hospitalization for heart failure by 25% versus placebo. These results were seen regardless of background heart failure standard of care treatments. A key secondary endpoint analysis from EMPEROR-Reduced demonstrated that Jardiance helped keep patients out of the hospital by significantly reducing the relative risk of first and recurrent hospitalization for heart failure by 30% (388 events for Jardiance vs. 553 for placebo).

The expansion of Jardiance for use in all heart failure patients was based on a randomized, double-blind, international trial comparing 2,997 patients  who received Jardiance, 10 mg, once daily to 2,991 participants who received the placebo. The main efficacy measurement was the time to death from cardiovascular causes or need to be hospitalized for heart failure. Of the individuals who received Jardiance for an average of about two years, 14% died from cardiovascular causes or were hospitalized for heart failure, compared to 17% of the participants who received the placebo.

Indication 4 - to reduce the risk of sustained decline in eGFR, end-stage kidney disease, cardiovascular death, and hospitalization in adults with chronic kidney disease at risk of progression

approved September 2023

Clinical Trial Results

FDA approval was based on EMPA-KIDNEY, a large trial in over 6,600 adults with CKD with or without type 2 diabetes. Patients included had an eGFR ≥20 to <45 mL/min/1.73 m2 or an eGFR ≥45 to <90 mL/min/1.73 m2 with a urine albumin to creatinine ratio ≥200 mg/g. Patients were excluded if they had both type 2 diabetes and prior atherosclerotic cardiovascular disease with eGFR below 60 mL/min/1.73 m2, had type 1 diabetes, had a functioning or scheduled kidney transplant, were on dialysis, had polycystic kidney disease, or required or had a recent history of intravenous immunosuppressive therapy or greater than 45 mg of prednisone or equivalent for kidney disease.

In EMPA-KIDNEY, Jardiance demonstrated a 28% relative risk reduction (absolute risk reduction 3.6% per patient-year at risk) compared with placebo, both on top of standard care, for the composite primary endpoint of kidney disease progression or cardiovascular death. The event rate for Jardiance was 13.1% (432/3304) and for placebo was 16.9% (558/3305). EMPA-KIDNEY is the first SGLT2 inhibitor CKD trial to demonstrate a significant reduction in the risk of first and recurrent hospitalization, a pre-specified key secondary endpoint, with a 14% relative risk reduction with Jardiance versus placebo. In the Jardiance group, 1,611 hospitalizations occurred among 960 patients (24.8 events per 100 patient-years). In the placebo group, 1,895 hospitalizations occurred among 1,035 patients (29.2 events per 100 patient-years).