PMID- 33941549 OWN - NLM STAT- MEDLINE DCOM- 20210621 LR - 20210621 IS - 2052-4897 (Electronic) IS - 2052-4897 (Linking) VI - 9 IP - 1 DP - 2021 May TI - Cost-effectiveness of empagliflozin versus canagliflozin, dapagliflozin, or standard of care in patients with type 2 diabetes and established cardiovascular disease. LID - 10.1136/bmjdrc-2020-001313 [doi] LID - e001313 AB - 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. CI - (c) Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Reifsnider, Odette S AU - Reifsnider OS AUID- ORCID: 0000-0003-0714-5619 AD - Evidera Inc, Bethesda, Maryland, USA odette.reifsnider@evidera.com. FAU - Kansal, Anuraag R AU - Kansal AR AD - Evidera Inc, Bethesda, Maryland, USA. FAU - Gandhi, Pranav K AU - Gandhi PK AD - Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut, USA. FAU - Cragin, Lael AU - Cragin L AD - Evidera Inc, Bethesda, Maryland, USA. FAU - Brand, Sarah B AU - Brand SB AD - Evidera Inc, Bethesda, Maryland, USA. FAU - Pfarr, Egon AU - Pfarr E AD - Boehringer Ingelheim Pharma GmbH and Co KG, Ingelheim, Rheinland-Pfalz, Germany. FAU - Fahrbach, Kyle AU - Fahrbach K AD - Evidera Waltham, Waltham, Massachusetts, USA. FAU - Ustyugova, Anastasia AU - Ustyugova A AD - Boehringer Ingelheim Pharma GmbH and Co KG, Ingelheim, Rheinland-Pfalz, Germany. LA - eng PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't PL - England TA - BMJ Open Diabetes Res Care JT - BMJ open diabetes research & care JID - 101641391 RN - 0 (Benzhydryl Compounds) RN - 0 (Glucosides) RN - 0 (Hypoglycemic Agents) RN - 0SAC974Z85 (Canagliflozin) RN - 1ULL0QJ8UC (dapagliflozin) RN - HDC1R2M35U (empagliflozin) SB - IM MH - Adult MH - Benzhydryl Compounds MH - Canagliflozin/therapeutic use MH - *Cardiovascular Diseases/epidemiology/prevention & control MH - Cost-Benefit Analysis MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Glucosides MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Standard of Care PMC - PMC8098979 OTO - NOTNLM OT - cardiovascular system OT - cost effectiveness OT - sodium glucose cotransporter OT - type 2 diabetes COIS- 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. EDAT- 2021/05/05 06:00 MHDA- 2021/06/22 06:00 PMCR- 2021/05/03 CRDT- 2021/05/04 06:24 PHST- 2020/02/25 00:00 [received] PHST- 2021/03/11 00:00 [revised] PHST- 2021/04/02 00:00 [accepted] PHST- 2021/05/04 06:24 [entrez] PHST- 2021/05/05 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2021/05/03 00:00 [pmc-release] AID - 9/1/e001313 [pii] AID - bmjdrc-2020-001313 [pii] AID - 10.1136/bmjdrc-2020-001313 [doi] PST - ppublish SO - BMJ Open Diabetes Res Care. 2021 May;9(1):e001313. doi: 10.1136/bmjdrc-2020-001313.