Article Text

Cost-effectiveness of empagliflozin versus canagliflozin, dapagliflozin, or standard of care in patients with type 2 diabetes and established cardiovascular disease
  1. Odette S Reifsnider1,
  2. Anuraag R Kansal1,
  3. Pranav K Gandhi2,
  4. Lael Cragin1,
  5. Sarah B Brand1,
  6. Egon Pfarr3,
  7. Kyle Fahrbach4,
  8. Anastasia Ustyugova3
  1. 1Evidera Inc, Bethesda, Maryland, USA
  2. 2Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut, USA
  3. 3Boehringer Ingelheim Pharma GmbH and Co KG, Ingelheim, Rheinland-Pfalz, Germany
  4. 4Evidera Waltham, Waltham, Massachusetts, USA
  1. Correspondence to Dr Odette S Reifsnider; odette.reifsnider{at}


Introduction Empagliflozin, a sodium-glucose co-transporter-2 (SGLT-2) inhibitor, is approved in the USA to reduce risk of cardiovascular (CV) death in adults with type 2 diabetes mellitus (T2DM) and established CV disease, based on EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) trial results. Empagliflozin reduced major adverse CV event (MACE) by 14%, CV death by 38%, and hospitalization for heart failure (HHF) by 35% vs placebo, each on top of standard of care (SoC). SGLT-2 inhibitors canagliflozin and dapagliflozin have also been compared with placebo, all on top of SoC, in CV outcome trials. In the CANVAS (Canagliflozin Cardiovascular Assessment Study) Program, canagliflozin reduced MACE by 14% and HHF by 33%. Dapagliflozin reduced HHF by 27% in the DECLARE-TIMI 58 trial (Multicenter Trial to Evaluate the Effect of Dapagliflozin on the Incidence of Cardiovascular Events). This analysis estimated the cost-effectiveness of empagliflozin versus canagliflozin, dapagliflozin, or SoC, in US adults with T2DM and established CV disease.

Research design and methods Individual patient-level discrete-event simulation was conducted to predict time-to-event for CV and renal outcomes, and specific adverse events over patients’ lifetimes. Occurrence of events in EMPA-REG OUTCOME was estimated based on event-free survival curves with time-dependent covariates. An HR for canagliflozin or dapagliflozin versus empagliflozin on each clinical event was estimated from published CANVAS, DECLARE-TIMI 58, and EMPA-REG OUTCOME data using indirect treatment comparison. Public sources provided US costs and utilities.

Results The model predicted longer survival for empagliflozin versus canagliflozin, dapagliflozin, and SoC mainly due to direct reduction in CV death. Empagliflozin dominated canagliflozin, yielding more quality-adjusted life years (QALYs; 0.38) at a lower cost (−US$306). Compared with dapagliflozin and SoC, empagliflozin yielded 0.50 and 0.84 incremental QALYs at US$1517 and US$27 539 incremental costs, yielding incremental cost-effectiveness ratios of US$3054/QALY and US$32 848/QALY, respectively.

Conclusions Empagliflozin was projected to dominate canagliflozin and be highly cost-effective compared with dapagliflozin and SoC using US healthcare costs.

  • type 2 diabetes
  • cost effectiveness
  • sodium glucose cotransporter
  • cardiovascular system

Data availability statement

Data are available on reasonable request. Our study data (which is based on de-identified data from a clinical trial) is not in a repository, but is available on reasonable request from the corresponding author (ORCiD 0000-0003-0714-5619).

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Data availability statement

Data are available on reasonable request. Our study data (which is based on de-identified data from a clinical trial) is not in a repository, but is available on reasonable request from the corresponding author (ORCiD 0000-0003-0714-5619).

View Full Text

Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.


  • Contributors All authors contributed to the interpretation of data and results and drafting the manuscript. Additionally, OSR, ARK, LC, and SBB contributed to the model development, identification of data sources, conduct of analyses, and implementation of the design. KF performed the indirect treatment comparison. PKG, EP, and AU reviewed the final model design, data sources, and results.

  • Funding Sponsorship for this study and article processing charges were funded by Boehringer Ingelheim Pharma GmbH & Co KG of Ingelheim am Rhein, Germany. All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis. Editorial assistance in the preparation of this article was provided by Janet Dooley of Evidera’s Editorial and Design Services team. Support for this assistance was funded by Boehringer Ingelheim Pharmaceuticals, Inc.

  • Competing interests OSR, SBB, and KF are employees of Evidera, which provides consulting and other research services to the biopharmaceutical industry. ARK and LC were employees of Evidera during the conduct of this study and development of this article, but are now employed elsewhere. In their salaried positions, Evidera employees work with a variety of companies and organizations, and are precluded from receiving any payment or honoraria directly from these organisations for services rendered. Evidera received funding from Boehringer Ingelheim Pharma GmbH & Co KG. EP and AU are current employees of Boehringer Ingelheim Pharma GmbH & Co. KG of Ingelheim am Rhein, Germany. PKG was an employee of Boehringer Ingelheim Pharmaceuticals, Inc. in Ridgefield, Connecticut, USA during the conduct of this study and development of this article, but he is now employed elsewhere.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.