Effectiveness and Safety of Empagliflozin in Routine Care: Results from the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) Study

Friday, August 26, 2022

6:15 PM – 6:20 PM CEST

Location: C1M2

Publication Number: 110

Background: Empagliflozin (EMPA) reduces the risk of cardiovascular outcomes in trials. The Empagliflozin Comparative Effectiveness and Safety (EMPRISE) is a 5-year monitoring program (2014-19) that evaluates the effectiveness and safety of EMPA using routine clinical care data.

Objectives: To evaluate the comparative cardiovascular effectiveness and safety of EMPA vs. dipeptidyl peptidase-4 inhibitors (DPP-4i) in patients with type 2 diabetes.

Methods: Using Medicare, Optum Clinformatics® Data Mart and IBM MarketScan® databases [2014-2019 (2018 for Medicare)], we identified patients ≥18 years with type 2 diabetes initiating EMPA or a DPP-4i. We identified primary outcomes of heart failure hospitalization in primary (HHF-Specific) or any discharge positions (HHF-Broad), a composite of hospitalizations for myocardial infarction (MI) and stroke, and all-cause mortality (ACM) (Medicare only), based on validated claims-based algorithms. Safety outcomes were lower-limb amputations (LLA), non-vertebral fractures, diabetic ketoacidosis (DKA), acute kidney injury (AKI), renal and bladder cancers (CA). We estimated HR (95% CI) and rate differences (RD) per 1,000 person-years after propensity score matching, pooled across 3 databases, adjusting for 143 baseline (365 days) covariates, and accounting for mortality as a competing risk. We conducted both as-treated analyses censoring for treatment changes, and intent-to-treat (ITT) without censoring for them.

Results: We identified 190,226 eligible patients and baseline characteristics were similar between EMPA vs. matched DPP-4i initiators. After matching, mean age of the cohort across 3 databases was approximately 60 years for both initiators. Median as-treated follow-up ranged from 6-7 months across the outcomes, with an approximate interquartile range of 3-10 months. Compared to DPP4i, EMPA was associated with a reduced risk of HHF-Specific [HR 0.47 (0.41, 0.55); RD -4.26 (-5.10, -3.44)] and HHF-Broad: [HR 0.67 (0.62, 0.72); RD -9.50 (-11.14, -7.88)], a similar risk of the composite of MI or stroke [HR 0.92 (0.84, 1.02); RD -1.24 (-2.45, -0.03)], and a reduced risk of ACM [HR 0.56 (0.46, 0.68); RD -2.69 (-3.53, -1.85)]. For safety outcomes, EMPA was associated with a reduced risk of AKI [HR 0.73 (0.68, 0.78); RD -8.68 (-10.43, -6.94)], an increased risk of DKA [HR 1.88 (1.51, 2.34); RD 1.65 (1.09, 2.23)], and a similar risk of LLA, fractures, and renal and bladder CA. The ITT analyses produced similar estimates.

Conclusions: Our findings support the cardiovascular effectiveness of EMPA in routine care with a safety profile in line with previously documented information.

Presenting Author(s)

Phyo T. Htoo

Brigham and Women's Hospital/Harvard Medical School
Boston, Massachusetts, United States

Slides

Co-Author(s)

HT

Helen Tesfaye

Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, United States
JP

Julie M. Paik, MD, ScD

Brigham and Women's Hospital, Harvard Medical School
Boston, Massachusetts, United States
DW

Deborah Wexler, MD MSc

Massachusetts General Hospital, MA, United States
MN

Mehdi Najafzadeh

Brigham and Women's Hospital, United States
RG

Robert Glynn, PhD, ScD

Harvard Medical School, Brigham and Women's Hospital
Boston, MA, United States
AD

Anouk Deruaz-Luyet

Boehringer Ingelheim International GmbH, Germany
SF

Soulmaz Farsani

Brigham and Women's Hospital, Germany
LK

Lisette Koeneman

Lilly Deutschland, Germany
Sebastian Schneeweiss, ScD, MD, FISPE

Professor of Medicine
BWH Div of Pharmacoepidemiology and Pharmacoeconomics
Boston, Massachusetts, United States
EP

Elisabetta Patorno

Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, United States