Jardiance Demonstrates Superior Efficacy in Reducing Heart Failure Hospitalization Risk Compared to DPP-4 Inhibitors and GLP-1 Receptor Agonists: Interim EMPRISE Real-World Study Results

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The Boehringer Ingelheim-Eli Lilly Diabetes Alliance recently announced the latest analysis of three-year data from the large-scale real-world study EMPRISE (NCT03363464) at the American Heart Association’s Annual Scientific Sessions 2019 held in Philadelphia. The results showed that,Compared with DPP-4 inhibitors and GLP-1 receptor agonists, Jardiance (empagliflozin) is associated with a reduced risk of hospitalization for heart failure and a similar risk of nonfatal atherosclerotic cardiovascular events.。

This study was initiated in 2016 with the aim of supplementing the findings of the EMPA-REG OUTCOME cardiovascular outcomes trial by providing comparisons with DPP-4 inhibitors in terms of efficacy, safety, healthcare resource utilization, and costs among patients with type 2 diabetes mellitus, both with and without cardiovascular disease. Furthermore, subgroup analyses provided data comparing the efficacy of Jardiance with that of GLP-1 receptor agonists.

This study will evaluate the use of Jardiance in the US market from 2014 to 2019. Data analysis includes planned interim analyses (with data updates every 12 months) and a final analysis. By the time the study is completed, the number of participants is expected to exceed 200,000. Starting in 2019, other EMPRISE studies, including those in Asia and Europe, will provide international insights into the use of Jardiance in routine clinical care across different regions of the world.

The three-year interim analysis data from the EMPRISE study are presented here, showing that:Compared with DPP-4 inhibitors and GLP-1 receptor agonists, Jardiance was associated with a 41% and 17% reduction in the risk of hospitalization for heart failure, respectively.The risk of nonfatal atherosclerotic cardiovascular events (defined as nonfatal myocardial infarction or stroke, hospitalization for unstable angina, or coronary revascularization) was similar in patients treated with Jardiance (14.6 events per 1,000 patient-years) and those treated with DPP-4 inhibitors (17.6 events per 1,000 patient-years). Furthermore, the risk was also similar between patients treated with Jardiance (14.2 events per 1,000 patient-years) and those treated with GLP-1 receptor agonists (14.8 events per 1,000 patient-years).

Previously, the second interim analysis of the EMPRISE study (including more than 45,000 patients) showed that Jardiance was associated with a significant reduction in all-cause hospitalizations, emergency room visits, and physician office visits compared with DPP-4 inhibitors.

Real-world findings from the EMPRISE study, derived from routine clinical care, complement the data from the landmark EMPA-REG OUTCOME trial. In that trial, among adult patients with type 2 diabetes and cardiovascular disease, Jardiance reduced the relative risk of hospitalization for heart failure by 35% compared with placebo. The EMPA-REG OUTCOME trial also demonstrated that, in the same population, Jardiance reduced the relative risk of cardiovascular death by 38% compared with placebo.

In Europe and the United States, heart failure is the most common cause of hospitalization among adults aged 65 years and older. Therefore, it is highly encouraging that Jardiance has been observed to reduce the risk of heart failure hospitalization in patients with type 2 diabetes not only in clinical trials but also in routine clinical practice. Furthermore, given that one in three patients with type 2 diabetes has cardiovascular disease, it is also very encouraging to observe similar results regarding the risk of non-fatal atherosclerotic cardiovascular events, as Jardiance has previously demonstrated favorable outcomes on this endpoint compared with other type 2 diabetes medications.

The active pharmaceutical ingredient of Jardiance is empagliflozin, a sodium-glucose cotransporter-2 (SGLT-2) inhibitor. The emerging class of SGLT-2 inhibitors has been proven to block glucose reabsorption in the kidneys, excreting excess glucose from the body, thereby lowering blood glucose levels. Moreover, this glucose-lowering effect is independent of β-cell function and insulin resistance.

Jardiance was approved for marketing in August 2014 for the treatment of patients with type 2 diabetes. In late 2016, Jardiance received further approval to reduce the risk of cardiovascular death in patients with type 2 diabetes and comorbid cardiovascular disease. This approval made Jardiance the first glucose-lowering drug globally approved to reduce the risk of cardiovascular death in patients with type 2 diabetes.

In recent years, Boehringer Ingelheim and Eli Lilly have been committed to expanding the indications for Jardiance, including heart failure and type 1 diabetes.

In the field of heart failure, the two parties are conducting a large-scale program, EMPEROR, to evaluate the impact of Jardiance on heart failure-related outcomes and functional capacity in patients with heart failure. The program comprises multiple studies involving more than 9,500 adult patients with heart failure, including those with and without diabetes. In late June this year, the U.S. FDA granted Fast Track designation to the EMPEROR program.

Regarding type 1 diabetes, the supplemental New Drug Application (sNDA) for empagliflozin 2.5 mg is under review by the FDA. Last week, the agency’s Endocrine and Metabolic Drugs Advisory Committee convened to review and discuss the sNDA. By a vote of 14:2, the committee concluded that the benefits of empagliflozin 2.5 mg as an adjunct to insulin therapy for adult patients with type 1 diabetes do not outweigh the risks, and that the data do not support its approval. (14:2! FDA Advisory Committee Opposes Use of Empagliflozin in Type 1 Diabetes)

Although the advisory committee’s vote is not binding on the FDA, the agency typically follows its recommendations when making final review decisions. This means that the new indication application for empagliflozin 2.5 mg in the treatment of type 1 diabetes is highly likely to be rejected by the FDA. However, even if rejected, the outcome would be expected. Previously, AstraZeneca’s SGLT2 inhibitor Farxiga and Sanofi/Lexicon’s dual SGLT1/2 inhibitor Zynquista were both rejected by the FDA but received regulatory approval in the European Union.

Reference Source:

1、Interim analysis from EMPRISE real-world study shows empagliflozin decreased risk of hospitalisation for heart failure compared with DPP-4 inhibitors and GLP-1 receptor agonists

2、Boehringer Ingelheim and Lilly announce outcome of FDA Advisory Committee meeting for empagliflozin 2.5 mg as adjunct to insulin for adults with type 1 diabetes

3、Boehringer Ingelheim and Lilly initiate first ever study to assess Jardiance? in people hospitalized for acute heart failure who have been stabilized