Industry Sponsor-funded real-world study called EMPagliflozin comparative effectiveness and SafEty (EMPRISE) reveals that empagliflozin was associated with a decreased risk of hospitalization for heart failure as well as similar risk of non-fatal atherosclerotic cardiovascular events compared with DPP-4 inhibitors and GLP-1 receptor agonists. This interim analysis included 190,000 U.S. adults with type 2 diabetes with and without cardiovascular disease. Both Boehringer Ingelheim and Eli Lilly and Company (LLY) shared the results at the American Heart Association® Scientific Sessions 2019 in Philadelphia, PA. The Real-world study reflects a partnership between Brigham and Women’s Hospital and Boehringer Ingelheim, the world’s largest privately-held biopharmaceutical company.
The EMPRISE Real-World Study
The sponsors found that in the new interim analysis empagliflozin was associated with a reduced risk of hospitalization for heart failure of 41% compared with DPP-4 inhibitors and of 17% compared with GLP-1 receptor antagonists.
In regard to risks for non-fatal atherosclerotic cardiovascular events—non-fatal heart attack of stroke, hospitalization for unstable angina or coronary revascularization—was similar for those treated with empagliflozin (14.6 events per 1,000 patient-years) compared with DPP-4 inhibitors (17.6 events per 1,000 patient-years). The risk was also similar for those treated with empagliflozin (14.2 events per 1,000 patient-years) compared with GLP-1 receptor antagonists (14.8 events per 1,000 patient years).
In a second interim analysis of EMPRISE, which included more than 45,000 patients, empagliflozin was associated with a significant reduction in all-cause hospitalizations, emergency department visits and physician’s office visits compared with DPP-4 inhibitors.
Real-World EMPRISE compared to EMPA-REG OUTCOME® Random Controlled Trial
The industry sponsors compared the results of the real-world EMPRISE study in routine clinical care with the EMPA-REG OUTCOME® trail where empagliflozin showed a 35% relative risk reduction in hospitalization for heart failure compared with placebo in adults with type 2 diabetes and established cardiovascular disease. The EMPA-REG OUTCOME® trial revealed a 38% relative risk reduction in cardiovascular death in those taking empagliflozin versus placebo in the same population.
The effects of empagliflozin on heart failure-related outcomes and functional capacity in people with heart failure are being evaluated in the empagliflozin heart failure program. The program includes more than 9,500 adults with heart failure, including those with and without diabetes, consists of the following studies: EMPOROR-Reduced, EMPOROR-Preserved, EMPERIAL-Reduced, EMPERIAL-Preserved, EMPULSE and EMPA-VISION studies.
EMPRISE was started in 2016 to complement the EMPA-REG OUTCOME® trial results by generating data on the comparative effectiveness, safety, healthcare resource utilization and costs in routine clinical care compared with DPP-4 inhibitors in people with type 2 diabetes with and without cardiovascular disease. The sponsors offered sub-group analysis has well on the effectiveness of empagliflozin compared with GLP-1 receptor agonists.
The study will assess the first five years of empagliflozin use in the U.S. between 2014 and 2019. Data analysis includes planned interim analyses (based on 12 -month data updates) and a final analysis. More than 200,000 people with type 2 diabetes are projected to participate in the EMPRISE trial by its completion. From 2019, additional EMPRISE studies, including Asia and Europe, will offer insights from different regions of the world with an international perspective on the use of empagliflozin in routine clinical care—an important activity as the drug may act differently in different populations.
Empagliflozin vs. the Competition
The drug Empagliflozin (Jardiance) is an oral, once daily, highly selective sodium glucose cotransporter 2 (SGLT2) inhibitor and the first type 2 diabetes medicine to include cardiovascular death risk reduction data in the label in several countries. The sponsors (Boehringer Ingelheim and Lilly) report that inhibition of SGL2 with empagliflozin in people with type 2 diabetes and high blood sugar levels prevents sugar being re-absorbed by the kidneys, leading to the excretion of excess sugar in the urine. The drug also prevents salt being reabsorbed, leading to increased excretion of salt from the body and reducing the fluid load of the body’s blood vessel system (i.e. intravascular volume). Empagliflozin induces changes to the sugar, salt and water metabolism in the body that may contribute to the reductions in cardiovascular death as observed in their EMPA-REG OUTCOME® trial.
Jardiance revenues grew significantly from 2017 to 2018 from $447.5m to $658.3m or 47%.
Sponsors Boehringer Ingelheim and Lilly are keen on showing that Empagliflozin is superior to DPP-4 inhibitors for example. These are a class of oral hypoglycemics that block the enzyme dipeptidyl pedidase-4 and are used to treat type 2 diabetes. A meta-analysis found no favorable effect of DPP-4 inhibitors on all-cause mortality, cardiovascular mortality, myocardial infarction or stroke in patients with type 2 diabetes for example.
In December, 2018 TrialSite News included an overview of the world’s top selling diabetes drugs. The world’s fastest growing diabetes drug as measured by revenue growth by end of 2018 was a GLP-1 agonist called Trulicity. For a comparison of Jardiance versus Trulicity, see here. It was reported from the REWIND trial that dulaglutide (Trulicity) helped to reduce heart events in adults with type 2 diabetes. Of course, the relevance of the recent EMPRISE data is that Empagliflozin does so a little more.
Thus far, it appears that the EMPRISE study is validating the EMPA-REG OUTCOME® random controlled trial that empagliflozin was associated with a decreased risk of hospitalization for heart failure as well as similar risk of non-fatal atherosclerotic cardiovascular events compared with DPP-4 inhibitors and GLP-1 receptor inhibitors.
Call to Action: TrialSite News will continue to monitor the ongoing studies associated with Empagliflozin.