Evidence map›Paper›PMID 42437918›Full record

ArticleCardiovascular diabetology2026

Cardiovascular outcomes of empagliflozin-GLP-1RA combination therapy in type 2 diabetes: EMPRISE study.

Phyo T Htoo, Hanseul Cho, Julie M Paik, Katsiaryna Bykov, Brendan M Everett, Robert J Glynn, Christina Shay, Niklas Schmedt, Deborah J Wexler, Elisabetta Patorno

Abstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Cardiovascular diabetology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Phyo T HtooDivision of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Hanseul ChoDivision of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Julie M PaikDivision of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Katsiaryna BykovDivision of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Brendan M EverettDivisions of Cardiovascular and Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Robert J GlynnDivision of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Christina ShayTA CRM, Boehringer Ingelheim International GmbH, Ingelheim, Germany.
Niklas SchmedtTA CRM, Boehringer Ingelheim International GmbH, Ingelheim, Germany.
Deborah J WexlerDiabetes Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Elisabetta PatornoDivision of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. epatorno@mednet.ucla.edu.ORCID http://orcid.org/0000-0002-8809-9898

Funding

Novel Approaches to Monitor the Safety and Effectiveness of Newly Marketed Diabetes Medications in Older Adults Considering Frailty and MultimorbidityK08AG055670 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI PATORNO, ELISABETTA · 2018 to 2021
$661k
Novel approaches to identify and quantify the impact of drug-drug interactions in older adults with diabetes, with a focus on multimorbidity and polypharmacyK01AG068365 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI BYKOV, KATSIARYNA · 2021 to 2025
$621k
American Diabetes Association 4-22-PDFPM-15FDA HHS U01 FD007213NIA NIH HHS K01 AG068365NIA NIH HHS K01AG068365NIA NIH HHS K08 AG055670NIA NIH HHS K08AG055670Patient-Centered Outcomes Research Institute DB-2020C2-20326U.S. Food and Drug Administration 5U01FD007213
6 · The paper itself

Abstract

backgroundEvidence on the cardiovascular benefits of combining empagliflozin with glucagon-like peptide-1 receptor agonists (GLP-1RA) is limited, derived primarily from indirect comparisons or subgroup analyses of cardiovascular outcome trials.

methodsWe conducted a cohort study emulating two comparative effectiveness trials using US healthcare databases (2013-2022), including federal Medicare and commercial claims data (Optum Clinformatics and MarketScan). Among adults with type 2 diabetes in routine care, we compared cardiovascular outcomes in patients initiating: (i) empagliflozin first, followed by augmentation with either GLP-1RA or dipeptidyl peptidase-4 inhibitors (DPP-4i), and (ii) GLP-1RA first, followed by augmentation with either empagliflozin or sulfonylureas. Primary outcomes were modified major adverse cardiovascular events (MACE; composite of myocardial infarction, stroke, and all-cause mortality) and a composite of hospitalization for heart failure (HHF) or all-cause mortality. We estimated hazard ratios (HR) and rate differences (RD) per 1,000 person-years with 95% confidence intervals (CI), adjusting for over 130 baseline covariates using propensity score matching weights.

resultsCompared with empagliflozin-DPP-4i initiators, empagliflozin-GLP-1RA was associated with lower risk of MACE [HR: 0.81 (95% CI: 0.67, 0.97); RD: -3.7 (-7.1, -0.2)] and lower HHF-mortality [HR: 0.61 (0.48, 0.77); RD: -6.6 (-9.3, -3.9)]. Compared with the GLP-1RA-sulfonylurea combination, the GLP-1RA-empagliflozin combination had lower risks of MACE [HR: 0.68 (0.56, 0.81); RD: -5.3 (-7.9, -2.6)] and HHF-mortality [HR: 0.62 (0.51, 0.76); RD: -3.7 (-6.1, -1.8)].

conclusionsIn US clinical practice, adding GLP-1RA to empagliflozin was associated with lower risks of MACE and HHF-mortality compared with adding DPP-4i. Among GLP-1RA initiators, adding empagliflozin was associated with lower cardiovascular risk than adding sulfonylureas, supporting potential additive cardiovascular benefits of GLP-1RA-empagliflozin combination therapy.

Indexed as

Benzhydryl CompoundsCardiovascular DiseasesDiabetes Mellitus, Type 2Dipeptidyl-Peptidase IV InhibitorsGlucagon-Like Peptide-1 Receptor AgonistsGlucosidesIncretinsSodium-Glucose Transporter 2 InhibitorsAgedBiomarkersDatabases, FactualDrug Therapy, CombinationFemaleGlucagon-Like Peptide-1 ReceptorHumansInsulin SecretagoguesBenzhydryl CompoundsBiomarkersDipeptidyl-Peptidase IV InhibitorsempagliflozinGLP1R protein, humanGlucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsGlucosidesIncretinsInsulin SecretagoguesSodium-Glucose Transporter 2 InhibitorsSulfonylurea CompoundsCardiovascular diseaseEmpagliflozinGlucagon-like peptide-1 receptor agonistHeart failureSodium-glucose cotransporter-2 inhibitorType 2 diabetes mellitus

Identifiers

PMID42437918
PMCPMC13644152

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.