Jardiance® (empagliflozin) is a prescription medicine used to reduce the risk of cardiovascular death plus hospitalisation in adults with heart failure with reduced ejection fraction (HFrEF). It is also used in addition to diet and exercise for improving blood glucose levels and reduce the risk of cardiovascular death in adults with type 2 diabetes (T2D).
Developed by Boehringer Ingelheim and Eli Lilly, the drug is available as pale yellow, bi-convex shaped film-coated tablets containing 10mg (round-shaped) or 25mg (oval-shaped) of empagliflozin.
Regulatory approvals for Jardiance
Jardiance was first approved as an adjunct to diet and exercise to improve glycaemic control in adults with T2D by the European Commission (EC) in May 2014 and by the US Food and Drug Administration (FDA) in August 2014.
In December 2016, the FDA expanded Jardiance’s label to reduce the risk of cardiovascular death in adult patients with T2D and cardiovascular disease. The EC included cardiovascular death reduction data in the drug’s label in January 2017.
In October 2020, a supplemental new drug application (sNDA) for Jardiance was submitted to the FDA for reducing the risk of cardiovascular death or hospitalisation for heart failure in adults with HFrEF. The sNDA was accepted for review in January 2021.
In August 2021, the FDA further approved Jardiance for reducing the risk of cardiovascular death and hospitalisation for heart failure in adults with HFrEF.
Jardiance is also being investigated for treating chronic kidney disease (CKD), having received fast track designation from the FDA for treating CKD in March 2020. The results of the ongoing EMPA-KIDNEY trial are expected in 2022.
The drug received marketing authorisation in Europe for symptomatic chronic HFrEF in June 2021, after a positive recommendation by the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) in May 2021.
HFrEF causes and symptoms
HFrEF, or systolic heart failure, is a complicated clinical condition characterised by structural or functional left ventricular dysfunction. It occurs when the heart muscle fails to contract effectively, resulting in 40% or less left ventricular ejection fraction (LVEF) or less blood being pumped out to the body than in a normal working heart.
More than half of all heart failure cases are caused by HFrEF. The condition is associated with inadequately oxygenated blood being supplied to tissues and organs.
HFrEF’s signs and symptoms include dyspnoea, oedema, tiredness and decreased tolerance for exercise.
Jardiance’s mechanism of action
Jardiance is a selective inhibitor of sodium-glucose co-transporter 2 (SGLT2), the primary transporter responsible for reabsorbing glucose from the glomerular filtrate and reintroducing it into blood circulation.
SGLT2 inhibition decreases the renal reabsorption of filtered glucose, causing kidneys to excrete glucose from the body through urine.
Jardiance also decreases sodium reabsorption while increasing sodium distribution to the distal tubule, which may impact several physiological processes such as lowering both the heart’s preload and afterload and decreasing sympathetic activity.
Clinical trials on Jardiance
Jardiance’s safety and efficacy for patients with heart failure and HFrEF were investigated in EMPEROR‐Reduced, an international, randomised, double-blind, Phase III clinical trial.
In the clinical study, 3,730 patients with or without T2D having chronic heart failure with 40% or less LVEF were enrolled and randomised to receive Jardiance (1,863) 10mg or placebo (1,867). These were then followed for 16 months.
The study’s composite primary endpoint was the time to the first event of cardiovascular death or hospitalisation for heart failure (HHF). The secondary endpoint was the occurrence of first and recurrent HHF.
Jardiance significantly reduced the risk of cardiovascular death or hospitalisation for heart failure by 25% compared to placebo. It was also found to be superior in reducing the occurrence of first and recurrent HHF by 30% compared to placebo.
The drug’s safety profile for the condition was consistent with its established safety profile. The most common adverse effects reported during the clinical study were urinary tract infections and female genital mycotic infections.
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