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Comparative Effectiveness of Empagliflozin vs Liraglutide or Sitagliptin in Older Adults With Diverse Patient Characteristics

IMPORTANCE: Limited evidence is available on the comparative effectiveness of empagliflozin vs alternative second-line glucose-lowering agents in patients with type 2 diabetes (T2D) receiving routine care who have a broad spectrum of cardiorenal risk. OBJECTIVE: To evaluate the association of empagl...

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Autores principales: Htoo, Phyo T., Tesfaye, Helen, Schneeweiss, Sebastian, Wexler, Deborah J., Everett, Brendan M., Glynn, Robert J., Kim, Seoyoung C., Najafzadeh, Mehdi, Koeneman, Lisette, Farsani, Soulmaz Fazeli, Déruaz-Luyet, Anouk, Paik, Julie M., Patorno, Elisabetta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Medical Association 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9585433/
https://www.ncbi.nlm.nih.gov/pubmed/36264574
http://dx.doi.org/10.1001/jamanetworkopen.2022.37606
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author Htoo, Phyo T.
Tesfaye, Helen
Schneeweiss, Sebastian
Wexler, Deborah J.
Everett, Brendan M.
Glynn, Robert J.
Kim, Seoyoung C.
Najafzadeh, Mehdi
Koeneman, Lisette
Farsani, Soulmaz Fazeli
Déruaz-Luyet, Anouk
Paik, Julie M.
Patorno, Elisabetta
author_facet Htoo, Phyo T.
Tesfaye, Helen
Schneeweiss, Sebastian
Wexler, Deborah J.
Everett, Brendan M.
Glynn, Robert J.
Kim, Seoyoung C.
Najafzadeh, Mehdi
Koeneman, Lisette
Farsani, Soulmaz Fazeli
Déruaz-Luyet, Anouk
Paik, Julie M.
Patorno, Elisabetta
author_sort Htoo, Phyo T.
collection PubMed
description IMPORTANCE: Limited evidence is available on the comparative effectiveness of empagliflozin vs alternative second-line glucose-lowering agents in patients with type 2 diabetes (T2D) receiving routine care who have a broad spectrum of cardiorenal risk. OBJECTIVE: To evaluate the association of empagliflozin with cardiovascular outcomes relative to liraglutide and sitagliptin, stratified by age, sex, baseline atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and chronic kidney disease (CKD). DESIGN, SETTING, AND PARTICIPANTS: This retrospective comparative effectiveness cohort study used deidentified Medicare claims data from August 1, 2014, to September 30, 2018, with follow-up from drug initiation until treatment changes, death, or gap in Medicare enrollment (>30 days). Data analysis was performed from October 1, 2021, to April 30, 2022. Medicare fee-for-service beneficiaries older than 65 years with T2D were included. A total of 45 788 patients (22 894 propensity score–matched pairs initiating treatment with either empagliflozin or liraglutide) were included in cohort 1, and 45 624 patients (22 812 propensity score–matched pairs initiating treatment with either empagliflozin or sitagliptin) were included in cohort 2. EXPOSURES: Empagliflozin vs liraglutide (cohort 1) or empagliflozin vs sitagliptin (cohort 2). MAIN OUTCOMES AND MEASURES: Primary outcomes were (1) modified major adverse cardiovascular events (MACEs), including a composite of myocardial infarction, stroke, and all-cause mortality, and (2) hospitalization for heart failure (HHF). Hazard ratios (HRs) and rate differences (RDs) per 1000 person-years were estimated, adjusting for 143 baseline covariates using 1:1 propensity score matching. RESULTS: Among 45 788 patients in cohort 1, the mean (SD) age was 71.9 (5.1) years; 23 396 patients (51.1%) were female, 22 392 (48.9%) were male, and 38 049 (83.1%) were White. Among 45 624 patients in cohort 2, the mean (SD) age was 72.1 (5.1) years; 21 418 patients (46.9%) were female, 24 206 (53.1%) were male, and 37 814 (82.9%) were White. Relative to patients initiating liraglutide, those initiating empagliflozin had a similar risk of the modified MACE outcome (HR, 0.90; 95% CI, 0.79-1.03) and a reduced risk of HHF (HR, 0.66; 95% CI, 0.52-0.82). Across subgroups, empagliflozin was associated with a lower risk of the modified MACE outcome in patients with a history of ASCVD (HR, 0.83; 95% CI, 0.71-0.98) and HF (HR, 0.77; 95% CI, 0.60-1.00) compared with liraglutide, and potential heterogeneity in estimates was observed by sex (male: HR, 0.85 [95% CI, 0.71-1.01]; female: HR, 1.16 [95% CI, 0.94-1.42]; P = .02 for homogeneity). However, reductions in the risk of HHF were observed across most subgroups (eg, ASCVD: HR, 0.66 [95% CI, 0.51-0.85]; HF: HR, 0.66 [95% CI, 0.49-0.88]). Compared with sitagliptin, empagliflozin was associated with reduced risks of the modified MACE outcome (HR, 0.68; 95% CI, 0.60-0.77) and HHF (HR, 0.45; 95% CI, 0.36-0.56), which were consistent across all subgroups. Absolute benefits of empagliflozin vs sitagliptin were larger in patients with a history of ASCVD (modified MACE: RD, −17.6 [95% CI, −24.9 to −10.4]; HHF: RD, −16.7 [95% CI, −21.7 to −11.9]), HF (modified MACE: RD, −41.1 [95% CI, −59.9 to −22.6]; HHF: RD, −50.4 [95% CI, −67.5 to −33.9]), or CKD (modified MACE: RD, −26.7 [95% CI, −41.3 to −12.3]; HHF: RD, −31.9 [95% CI, −43.5 to −20.8]). CONCLUSIONS AND RELEVANCE: In this comparative effectiveness study of older adults, empagliflozin was associated with a lower risk of HHF (relative to both liraglutide and sitagliptin) and the modified MACE outcome (relative to sitagliptin), with larger absolute benefits in patients with established cardiorenal diseases. These findings suggest that older adults with T2D might benefit more from empagliflozin vs liraglutide or sitagliptin with respect to the risk of HHF; with respect to the risk of MACEs, empagliflozin might be preferable to liraglutide only in patients with cardiovascular disease history and to sitagliptin across all patient subgroups.
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spelling pubmed-95854332022-11-04 Comparative Effectiveness of Empagliflozin vs Liraglutide or Sitagliptin in Older Adults With Diverse Patient Characteristics Htoo, Phyo T. Tesfaye, Helen Schneeweiss, Sebastian Wexler, Deborah J. Everett, Brendan M. Glynn, Robert J. Kim, Seoyoung C. Najafzadeh, Mehdi Koeneman, Lisette Farsani, Soulmaz Fazeli Déruaz-Luyet, Anouk Paik, Julie M. Patorno, Elisabetta JAMA Netw Open Original Investigation IMPORTANCE: Limited evidence is available on the comparative effectiveness of empagliflozin vs alternative second-line glucose-lowering agents in patients with type 2 diabetes (T2D) receiving routine care who have a broad spectrum of cardiorenal risk. OBJECTIVE: To evaluate the association of empagliflozin with cardiovascular outcomes relative to liraglutide and sitagliptin, stratified by age, sex, baseline atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and chronic kidney disease (CKD). DESIGN, SETTING, AND PARTICIPANTS: This retrospective comparative effectiveness cohort study used deidentified Medicare claims data from August 1, 2014, to September 30, 2018, with follow-up from drug initiation until treatment changes, death, or gap in Medicare enrollment (>30 days). Data analysis was performed from October 1, 2021, to April 30, 2022. Medicare fee-for-service beneficiaries older than 65 years with T2D were included. A total of 45 788 patients (22 894 propensity score–matched pairs initiating treatment with either empagliflozin or liraglutide) were included in cohort 1, and 45 624 patients (22 812 propensity score–matched pairs initiating treatment with either empagliflozin or sitagliptin) were included in cohort 2. EXPOSURES: Empagliflozin vs liraglutide (cohort 1) or empagliflozin vs sitagliptin (cohort 2). MAIN OUTCOMES AND MEASURES: Primary outcomes were (1) modified major adverse cardiovascular events (MACEs), including a composite of myocardial infarction, stroke, and all-cause mortality, and (2) hospitalization for heart failure (HHF). Hazard ratios (HRs) and rate differences (RDs) per 1000 person-years were estimated, adjusting for 143 baseline covariates using 1:1 propensity score matching. RESULTS: Among 45 788 patients in cohort 1, the mean (SD) age was 71.9 (5.1) years; 23 396 patients (51.1%) were female, 22 392 (48.9%) were male, and 38 049 (83.1%) were White. Among 45 624 patients in cohort 2, the mean (SD) age was 72.1 (5.1) years; 21 418 patients (46.9%) were female, 24 206 (53.1%) were male, and 37 814 (82.9%) were White. Relative to patients initiating liraglutide, those initiating empagliflozin had a similar risk of the modified MACE outcome (HR, 0.90; 95% CI, 0.79-1.03) and a reduced risk of HHF (HR, 0.66; 95% CI, 0.52-0.82). Across subgroups, empagliflozin was associated with a lower risk of the modified MACE outcome in patients with a history of ASCVD (HR, 0.83; 95% CI, 0.71-0.98) and HF (HR, 0.77; 95% CI, 0.60-1.00) compared with liraglutide, and potential heterogeneity in estimates was observed by sex (male: HR, 0.85 [95% CI, 0.71-1.01]; female: HR, 1.16 [95% CI, 0.94-1.42]; P = .02 for homogeneity). However, reductions in the risk of HHF were observed across most subgroups (eg, ASCVD: HR, 0.66 [95% CI, 0.51-0.85]; HF: HR, 0.66 [95% CI, 0.49-0.88]). Compared with sitagliptin, empagliflozin was associated with reduced risks of the modified MACE outcome (HR, 0.68; 95% CI, 0.60-0.77) and HHF (HR, 0.45; 95% CI, 0.36-0.56), which were consistent across all subgroups. Absolute benefits of empagliflozin vs sitagliptin were larger in patients with a history of ASCVD (modified MACE: RD, −17.6 [95% CI, −24.9 to −10.4]; HHF: RD, −16.7 [95% CI, −21.7 to −11.9]), HF (modified MACE: RD, −41.1 [95% CI, −59.9 to −22.6]; HHF: RD, −50.4 [95% CI, −67.5 to −33.9]), or CKD (modified MACE: RD, −26.7 [95% CI, −41.3 to −12.3]; HHF: RD, −31.9 [95% CI, −43.5 to −20.8]). CONCLUSIONS AND RELEVANCE: In this comparative effectiveness study of older adults, empagliflozin was associated with a lower risk of HHF (relative to both liraglutide and sitagliptin) and the modified MACE outcome (relative to sitagliptin), with larger absolute benefits in patients with established cardiorenal diseases. These findings suggest that older adults with T2D might benefit more from empagliflozin vs liraglutide or sitagliptin with respect to the risk of HHF; with respect to the risk of MACEs, empagliflozin might be preferable to liraglutide only in patients with cardiovascular disease history and to sitagliptin across all patient subgroups. American Medical Association 2022-10-20 /pmc/articles/PMC9585433/ /pubmed/36264574 http://dx.doi.org/10.1001/jamanetworkopen.2022.37606 Text en Copyright 2022 Htoo PT et al. JAMA Network Open. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the CC-BY License.
spellingShingle Original Investigation
Htoo, Phyo T.
Tesfaye, Helen
Schneeweiss, Sebastian
Wexler, Deborah J.
Everett, Brendan M.
Glynn, Robert J.
Kim, Seoyoung C.
Najafzadeh, Mehdi
Koeneman, Lisette
Farsani, Soulmaz Fazeli
Déruaz-Luyet, Anouk
Paik, Julie M.
Patorno, Elisabetta
Comparative Effectiveness of Empagliflozin vs Liraglutide or Sitagliptin in Older Adults With Diverse Patient Characteristics
title Comparative Effectiveness of Empagliflozin vs Liraglutide or Sitagliptin in Older Adults With Diverse Patient Characteristics
title_full Comparative Effectiveness of Empagliflozin vs Liraglutide or Sitagliptin in Older Adults With Diverse Patient Characteristics
title_fullStr Comparative Effectiveness of Empagliflozin vs Liraglutide or Sitagliptin in Older Adults With Diverse Patient Characteristics
title_full_unstemmed Comparative Effectiveness of Empagliflozin vs Liraglutide or Sitagliptin in Older Adults With Diverse Patient Characteristics
title_short Comparative Effectiveness of Empagliflozin vs Liraglutide or Sitagliptin in Older Adults With Diverse Patient Characteristics
title_sort comparative effectiveness of empagliflozin vs liraglutide or sitagliptin in older adults with diverse patient characteristics
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9585433/
https://www.ncbi.nlm.nih.gov/pubmed/36264574
http://dx.doi.org/10.1001/jamanetworkopen.2022.37606
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