Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Cardiovascular Diabetology
Published in: Cardiovascular Diabetology 1/2024

Open Access 01-12-2024 | Empagliflozin | Research

Cardiorenal effectiveness of empagliflozin vs. glucagon-like peptide-1 receptor agonists: final-year results from the EMPRISE study

Authors: Phyo T. Htoo, Helen Tesfaye, Sebastian Schneeweiss, Deborah J. Wexler, Brendan M. Everett, Robert J. Glynn, Niklas Schmedt, Lisette Koeneman, Anouk Déruaz-Luyet, Julie M. Paik, Elisabetta Patorno

Published in: Cardiovascular Diabetology | Issue 1/2024

Login to get access

Abstract

Background

No randomized clinical trials have directly compared the cardiorenal effectiveness of empagliflozin and GLP-1RA agents with demonstrated cardioprotective effects in patients with a broad spectrum of cardiovascular risk. We reported the final-year results of the EMPRISE study, a monitoring program designed to evaluate the cardiorenal effectiveness of empagliflozin across broad patient subgroups.

Methods

We identified patients ≥ 18 years old with type 2 diabetes who initiated empagliflozin or GLP-1RA from 2014 to 2019 using US Medicare and commercial claims databases. After 1:1 propensity score matching using 143 baseline characteristics, we evaluated risks of outcomes including myocardial infarction (MI) or stroke, hospitalization for heart failure (HHF), major adverse cardiovascular events (MACE – MI, stroke, or cardiovascular mortality), a composite of HHF or cardiovascular mortality, and progression to end-stage kidney disease (ESKD) (in patients with chronic kidney disease stages 3–4). We estimated hazard ratios (HR) and rate differences (RD) per 1,000 person-years, overall and within subgroups of age, sex, baseline atherosclerotic cardiovascular disease (ASCVD), and heart failure (HF).

Results

We identified 141,541 matched pairs. Compared with GLP-1RA, empagliflozin was associated with similar risks of MI or stroke [HR: 0.99 (0.92, 1.07); RD: -0.23 (-1.25, 0.79)], and lower risks of HHF [HR: 0.50 (0.44, 0.56); RD: -2.28 (-2.98, -1.59)], MACE [HR: 0.90 (0.82, 0.99); RD: -2.54 (-4.76, -0.32)], cardiovascular mortality or HHF [HR: 0.77 (0.69, 0.86); RD: -4.11 (-5.95, -2.29)], and ESKD [0.75 (0.60, 0.94); RD: -6.77 (-11.97, -1.61)]. Absolute risk reductions were larger in older patients and in those with baseline ASCVD/HF. They did not differ by sex.

Conclusions

The cardiovascular benefits of empagliflozin vs. cardioprotective GLP-1RA agents were larger in older patients and in patients with history of ASCVD or HF, while they did not differ by sex. In patients with advanced CKD, empagliflozin was associated with risk reductions of progression to ESKD.
Appendix
Available only for authorised users
Literature
1.
Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, et al. Empagliflozin, Cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–28.CrossRefPubMed
2.
Sattar N, Lee MMY, Kristensen SL, Branch KRH, Del Prato S, Khurmi NS, Lam CSP, Lopes RD, McMurray JJV, Pratley RE, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials. Lancet Diabetes Endocrinol. 2021;9(10):653–62.CrossRefPubMed
3.
Zelniker TA, Wiviott SD, Raz I, Im K, Goodrich EL, Bonaca MP, Mosenzon O, Kato ET, Cahn A, Furtado RHM, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet. 2019;393(10166):31–9.CrossRefPubMed
4.
McGuire DK, Shih WJ, Cosentino F, Charbonnel B, Cherney DZI, Dagogo-Jack S, Pratley R, Greenberg M, Wang S, Huyck S, et al. Association of SGLT2 inhibitors with Cardiovascular and kidney outcomes in patients with type 2 diabetes. JAMA Cardiol. 2021;6(2):148.CrossRefPubMed
5.
Patorno E, Pawar A, Bessette LG, Kim DH, Dave C, Glynn RJ, Munshi MN, Schneeweiss S, Wexler DJ, Kim SC. Comparative effectiveness and safety of sodium–glucose cotransporter 2 inhibitors Versus Glucagon-Like peptide 1 receptor agonists in older adults. Diabetes Care. 2021;44(3):826–35.CrossRefPubMedPubMedCentral
6.
Patorno E, Htoo P, Glynn RJ, Schneeweiss S, Wexler DJ, Pawar A, Bessette LG, Chin K, Everett BM, Kim SC. Sodium–glucose Cotransporter-2 inhibitors Versus Glucagon-like Peptide-1 receptor agonists and the risk for Cardiovascular outcomes in Routine Care patients with diabetes across categories of Cardiovascular Disease. Ann Intern Med. 2021;174:1528–41.CrossRefPubMedPubMedCentral
7.
Htoo PT, Buse J, Cavender M, Wang T, Pate V, Edwards J, Stürmer T. Cardiovascular effectiveness of sodium-glucose cotransporter 2 inhibitors and Glucagon‐like Peptide‐1 receptor agonists in older patients in Routine Clinical Care with or without history of atherosclerotic Cardiovascular diseases or Heart failure. J Am Heart Association 2022, 11(4).
8.
Nørgaard CH, Starkopf L, Gerds TA, Vestergaard P, Bonde AN, Fosbøl E, Køber L, Wong ND, Torp-Pedersen C, Lee CJ-Y. Cardiovascular outcomes with GLP-1 receptor agonists vs. SGLT-2 inhibitors in patients with type 2 diabetes. Eur Heart J - Cardiovasc Pharmacotherapy. 2021;8(6):549–56.CrossRef
9.
Ueda P, Wintzell V, Dahlqwist E, Eliasson B, Svensson AM, Franzén S, Gudbjörnsdottir S, Hveem K, Jonasson C, Melbye M et al. The comparative cardiovascular and renal effectiveness of sodium-glucose co‐transporter‐2 inhibitors and glucagon‐like peptide‐1 receptor agonists: a scandinavian cohort study. Diabetes Obes Metabolism 2021.
10.
Dong YH, Chang CH, Lin JW, Yang WS, Wu LC, Toh S. Comparative cardiovascular effectiveness of glucagon-like peptide-1 receptor agonists versus sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes: a population-based cohort study. Diabetes Obes Metab. 2022;24(8):1623–37.CrossRefPubMed
11.
Longato E, Di Camillo B, Sparacino G, Gubian L, Avogaro A, Fadini GP. Cardiovascular outcomes of type 2 diabetic patients treated with SGLT-2 inhibitors versus GLP-1 receptor agonists in real-life. BMJ Open Diabetes Res Care. 2020;8(1):e001451.CrossRefPubMedPubMedCentral
12.
Kim CH, Hwang I-C, Choi H-M, Ahn CH, Yoon YE, Cho G-Y. Differential cardiovascular and renal benefits of SGLT2 inhibitors and GLP1 receptor agonists in patients with type 2 diabetes mellitus. Int J Cardiol. 2022;364:104–11.CrossRefPubMed
13.
Baviera M, Foresta A, Colacioppo P, Macaluso G, Roncaglioni MC, Tettamanti M, Fortino I, Genovese S, Caruso I, Giorgino F. Effectiveness and safety of GLP-1 receptor agonists versus SGLT-2 inhibitors in type 2 diabetes: an Italian cohort study. Cardiovasc Diabetol 2022, 21(1).
14.
Tang EHM, Wong CKH, Lau KTK, Fei Y, Cheung BMY. Cardio-renal outcomes and the direct medical cost of type 2 diabetes patients treated with sodium glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists: a population-based cohort study. Diabetes Res Clin Pract. 2021;180:109071.CrossRefPubMed
15.
Pineda ED, Liao IC, Godley PJ, Michel JB, Rascati KL. Cardiovascular outcomes among patients with type 2 diabetes newly initiated on sodium-glucose Cotransporter-2 inhibitors, Glucagon-Like Peptide-1 receptor agonists, and other antidiabetic medications. J Managed Care Specialty Pharm. 2020;26(5):610–8.CrossRef
16.
Lugner M, Sattar N, Miftaraj M, Ekelund J, Franzén S, Svensson A-M, Eliasson B. Cardiorenal and other diabetes related outcomes with SGLT-2 inhibitors compared to GLP-1 receptor agonists in type 2 diabetes: nationwide observational study. Cardiovasc Diabetol 2021, 20(1).
17.
Poonawalla IB, Bowe AT, Tindal MC, Meah YA, Schwab P. A real-world comparison of cardiovascular, medical and costs outcomes in new users of SGLT2 inhibitors versus GLP-1 agonists. Diabetes Res Clin Pract. 2021;175:108800.CrossRefPubMed
18.
Fu EL, Clase CM, Janse RJ, Lindholm B, Dekker FW, Jardine MJ, Carrero J-J. Comparative effectiveness of SGLT2i versus GLP1-RA on cardiovascular outcomes in routine clinical practice. Int J Cardiol. 2022;352:172–9.CrossRefPubMed
19.
Htoo PT, Tesfaye H, Schneeweiss S, Wexler DJ, Everett BM, Glynn RJ, Kim SC, Najafzadeh M, Koeneman L, Farsani SF, et al. Comparative effectiveness of Empagliflozin vs Liraglutide or Sitagliptin in older adults with diverse patient characteristics. JAMA Netw Open. 2022;5(10):e2237606.CrossRefPubMedPubMedCentral
20.
Thomsen RW, Knudsen JS, Kahlert J, Baggesen LM, Lajer M, Holmgaard PH, Vedin O, Ustyugova A, Sørensen HT. Cardiovascular events, Acute hospitalizations, and mortality in patients with type 2 diabetes Mellitus who initiate Empagliflozin Versus Liraglutide: a comparative effectiveness study. J Am Heart Association 2021, 10(11).
21.
Patorno E, Najafzadeh M, Pawar A, Franklin JM, Déruaz-Luyet A, Brodovicz KG, Santiago Ortiz AJ, Bessette LG, Kulldorff M, Schneeweiss S. The EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study programme: design and exposure accrual for an evaluation of empagliflozin in routine clinical care. Endocrinol Diabetes Metabolism 2020, 3(1).
22.
Ray WA. Evaluating Medication effects outside of clinical trials: new-user designs. Am J Epidemiol. 2003;158(9):915–20.CrossRefPubMed
23.
Paik JM, Patorno E, Zhuo M, Bessette LG, York C, Gautam N, Kim DH, Kim SC. Accuracy of identifying diagnosis of moderate to severe chronic kidney disease in administrative claims data. Pharmacoepidemiol Drug Saf. 2022;31(4):467–75.CrossRefPubMed
24.
Jones SA, Gottesman RF, Shahar E, Wruck L, Rosamond WD. Validity of hospital discharge diagnosis codes for stroke: the atherosclerosis risk in communities Study. Stroke. 2014;45(11):3219–25.CrossRefPubMedPubMedCentral
25.
Kiyota Y, Schneeweiss S, Glynn RJ, Cannuscio CC, Avorn J, Solomon DH. Accuracy of Medicare claims-based diagnosis of acute myocardial infarction: estimating positive predictive value on the basis of review of hospital records. Am Heart J. 2004;148(1):99–104.CrossRefPubMed
26.
Birman-Deych E, Waterman AD, Yan Y, Nilasena DS, Radford MJ, Gage BF. Accuracy of ICD-9-CM codes for identifying cardiovascular and stroke risk factors. Med Care. 2005;43(5):480–5.CrossRefPubMed
27.
Hill ME, Rosenwaike I. The Social Security Administration’s death Master file: the completeness of death reporting at older ages. Soc Secur Bull. 2001;64(1):45–51.PubMed
28.
29.
Olubowale OT, Safford MM, Brown TM, Durant RW, Howard VJ, Gamboa C, Glasser SP, Rhodes JD, Levitan EB. Comparison of Expert Adjudicated Coronary Heart Disease and Cardiovascular Disease Mortality with the National Death Index: results from the REasons for Geographic and racial differences in stroke (REGARDS) study. J Am Heart Association. 2017;6(5):e004966.CrossRef
30.
Gagne JJ, Glynn RJ, Avorn J, Levin R, Schneeweiss S. A combined comorbidity score predicted mortality in elderly patients better than existing scores. J Clin Epidemiol. 2011;64(7):749–59.CrossRefPubMedPubMedCentral
31.
Kim DH, Patorno E, Pawar A, Lee H, Schneeweiss S, Glynn RJ. Measuring Frailty in Administrative Claims Data: comparative performance of four claims-based Frailty measures in the U.S. Medicare Data. J Gerontol Biol Sci Med Sci. 2020;75(6):1120–5.CrossRef
32.
Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika. 1983;70(1):41–55.MathSciNetCrossRef
33.
Ripollone JE, Huybrechts KF, Rothman KJ, Ferguson RE, Franklin JM. Implications of the Propensity score matching Paradox in Pharmacoepidemiology. Am J Epidemiol. 2018;187(9):1951–61.CrossRefPubMedPubMedCentral
34.
35.
Franklin JM, Rassen JA, Ackermann D, Bartels DB, Schneeweiss S. Metrics for covariate balance in cohort studies of causal effects. Stat Med. 2014;33(10):1685–99.MathSciNetCrossRefPubMed
36.
Schneeweiss S, Gagne JJ, Glynn RJ, Ruhl M, Rassen JA. Assessing the comparative effectiveness of newly marketed medications: methodological challenges and implications for drug development. Clin Pharmacol Ther. 2011;90(6):777–90.CrossRefPubMed
37.
American Diabetes A. Standards of Medical Care in Diabetes—2017 abridged for primary care providers. Clin Diabetes. 2017;35(1):5–26.CrossRef
38.
American Diabetes A. Standards of Medical Care in Diabetes—2018 abridged for primary care providers. Clin Diabetes. 2018;36(1):14–37.CrossRef
39.
Lash TL, Rothman KJ, VanderWeele TJ, Haneuse S. Modern Epidemiology: Wolters Kluwer; 2020.
40.
ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, Collins BS, Hilliard ME, Isaacs D, Johnson EL, et al. 9. Pharmacologic approaches to Glycemic Treatment: standards of Care in Diabetes—2023. Diabetes Care. 2022;46(Supplement1):140–S157.
41.
Schneeweiss S, Rassen JA, Glynn RJ, Avorn J, Mogun H, Brookhart MA. High-dimensional propensity score adjustment in studies of treatment effects using health care claims data. Epidemiology. 2009;20(4):512–22.CrossRefPubMedPubMedCentral
42.
Schneeweiss S. Sensitivity analysis and external adjustment for unmeasured confounders in epidemiologic database studies of therapeutics. Pharmacoepidemiol Drug Saf. 2006;15(5):291–303.CrossRefPubMed
43.
Wang SV, Sreedhara SK, Schneeweiss S, Franklin JM, Gagne JJ, Huybrechts KF, Patorno E, Jin Y, Lee M, Mahesri M et al. Reproducibility of real-world evidence studies using clinical practice data to inform regulatory and coverage decisions. Nat Commun 2022, 13(1).
44.
The EMPA-KIDNEY Collaborative Group. Empagliflozin in patients with chronic kidney disease. N Engl J Med. 2022;388(2):117–27.CrossRefPubMedCentral
45.
46.
Patorno E, Gopalakrishnan C, Franklin JM, Brodovicz KG, Masso-Gonzalez E, Bartels DB, Liu J, Schneeweiss S. Claims-based studies of oral glucose-lowering medications can achieve balance in critical clinical variables only observed in electronic health records. Diabetes Obes Metab. 2018;20(4):974–84.CrossRefPubMedPubMedCentral
Metadata
Title
Cardiorenal effectiveness of empagliflozin vs. glucagon-like peptide-1 receptor agonists: final-year results from the EMPRISE study
Authors
Phyo T. Htoo
Helen Tesfaye
Sebastian Schneeweiss
Deborah J. Wexler
Brendan M. Everett
Robert J. Glynn
Niklas Schmedt
Lisette Koeneman
Anouk Déruaz-Luyet
Julie M. Paik
Elisabetta Patorno
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2024
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-024-02150-0

Other articles of this Issue 1/2024

Cardiovascular Diabetology 1/2024 Go to the issue

Research

Insulin resistance and coronary inflammation in patients with coronary artery disease: a cross-sectional study

Research

Prognostic value of metabolic dysfunction-associated steatotic liver disease over coronary computed tomography angiography findings: comparison with no-alcoholic fatty liver disease

Research

Non-alcoholic fatty liver disease biomarkers estimate cardiovascular risk based on coronary artery calcium score in type 2 diabetes: a cross-sectional study with two independent cohorts

Research

Comparison of triglyceride glucose index and modified triglyceride glucose indices in prediction of cardiovascular diseases in middle aged and older Chinese adults

Research

Association of the triglyceride-glucose index with all-cause and cardiovascular mortality in patients with cardiometabolic syndrome: a national cohort study

Research

Abnormal vascular thickness and stiffness in young adults with type 1 diabetes: new insights from cutting-edge ultrasound modalities
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits