TY - JOUR

T1 - The comparative cardiovascular and renal effectiveness of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists

T2 - A Scandinavian cohort study

AU - Ueda, Peter

AU - Wintzell, Viktor

AU - Dahlqwist, Elisabeth

AU - Eliasson, Björn

AU - Svensson, Ann Marie

AU - Franzén, Stefan

AU - Gudbjörnsdottir, Soffia

AU - Hveem, Kristian

AU - Jonasson, Christian

AU - Melbye, Mads

AU - Hviid, Anders

AU - Svanström, Henrik

AU - Pasternak, Björn

N1 - Funding Information: All authors completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available upon request from the corresponding author) and have the following declarations. CJ reports personal fees from Pfizer and Bayer outside the submitted work. BE reports personal fees from Amgen, AstraZeneca, Boerhringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Mundipharma, Navamedic, Novo Nordisk, and RLS Global outside the submitted work, and grants from Sanofi outside the submitted work. SG reports lecture fees and research grants from AstraZeneca, Boerhringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Novo Nordisk, and Sanofi outside the submitted work. HS reports consulting fees from Celgene and employment at IQVIA outside the submitted work. The other authors did not have any potential conflicts to report. Funding Information: PU was supported by grants from the Swedish Heart‐Lung Foundation, the Swedish Society for Medical Research, and a faculty‐funded career position at Karolinska Institutet. BP was supported by an investigator grant from the Strategic Research Area Epidemiology programme at Karolinska Institutet. AH was supported by a Data Science Investigator grant from the Novo Nordisk Foundation. The study was conducted with research grant support from the Swedish Heart‐Lung Foundation and the Swedish Diabetes Foundation. The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Publisher Copyright: © 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

PY - 2022

Y1 - 2022

N2 - Aim: To assess the comparative cardiovascular and renal effectiveness of sodium-glucose co-transporter-2 (SGLT2) inhibitors versus glucagon-like peptide-1 (GLP-1) receptor agonists in routine clinical practice. Materials and Methods: A cohort study of nationwide registers from Sweden, Denmark, and Norway, including 87 525 new users of SGLT2 inhibitors and 63 921 new users of GLP-1 receptor agonists, was conducted using data from 2013-2018. Co-primary outcomes, analysed using an intention-to-treat exposure definition, were major adverse cardiovascular events (MACE; myocardial infarction, stroke, and cardiovascular death), heart failure (hospitalization or death because of heart failure), and serious renal events (renal replacement therapy, hospitalization for renal events, and death from renal causes). Results: Use of SGLT2 inhibitors versus GLP-1 receptor agonists was associated with a higher risk of MACE (adjusted incidence rate: 15.2 vs. 14.4 events per 1000 person-years; HR 1.07 [95% CI 1.01-1.15]), a similar risk of heart failure (6.0 vs. 6.0 events per 1000 person-years; HR 1.02 [0.92-1.12]), and a lower risk of serious renal events (2.9 vs. 4.0 events per 1000 person-years; HR 0.76 [0.66-0.87]). In as-treated analyses, the HR (95% CI) was 1.11 (1.00-1.24) for MACE, 0.88 (0.74-1.04) for heart failure, and 0.60 (0.47-0.77) for serious renal events. In secondary outcome analyses, use of SGLT2 inhibitors versus GLP-1 receptor agonists was not associated with statistically significant differences for the risk of myocardial infarction (HR 1.09 [95% CI 1.00-1.19]), cardiovascular death (HR 0.97 [95% CI 0.84-1.12]), death from renal causes (HR 0.75 [95% CI 0.41-1.35]), or any cause death (HR 1.01 [95% CI 0.94-1.09]), while the risk of stroke was higher (HR 1.14 [95% CI 1.03-1.26]), and the risk of renal replacement therapy (HR 0.74 [95% CI 0.56-0.97]) and hospitalization for renal events (HR 0.75 [95% CI 0.65-0.88]) were lower among users of SGLT2 inhibitors. Conclusions: Use of SGLT2 inhibitors versus GLP-1 receptor agonists was associated with a similar risk of heart failure and a lower risk of serious renal events, while use of GLP-1 receptor agonists versus SGLT2 inhibitors was associated with a slightly lower risk of MACE. In as-treated analyses, the associations with MACE and serious renal events increased in magnitude, and the HR for heart failure tended towards a protective association for SGLT2 inhibitors.

AB - Aim: To assess the comparative cardiovascular and renal effectiveness of sodium-glucose co-transporter-2 (SGLT2) inhibitors versus glucagon-like peptide-1 (GLP-1) receptor agonists in routine clinical practice. Materials and Methods: A cohort study of nationwide registers from Sweden, Denmark, and Norway, including 87 525 new users of SGLT2 inhibitors and 63 921 new users of GLP-1 receptor agonists, was conducted using data from 2013-2018. Co-primary outcomes, analysed using an intention-to-treat exposure definition, were major adverse cardiovascular events (MACE; myocardial infarction, stroke, and cardiovascular death), heart failure (hospitalization or death because of heart failure), and serious renal events (renal replacement therapy, hospitalization for renal events, and death from renal causes). Results: Use of SGLT2 inhibitors versus GLP-1 receptor agonists was associated with a higher risk of MACE (adjusted incidence rate: 15.2 vs. 14.4 events per 1000 person-years; HR 1.07 [95% CI 1.01-1.15]), a similar risk of heart failure (6.0 vs. 6.0 events per 1000 person-years; HR 1.02 [0.92-1.12]), and a lower risk of serious renal events (2.9 vs. 4.0 events per 1000 person-years; HR 0.76 [0.66-0.87]). In as-treated analyses, the HR (95% CI) was 1.11 (1.00-1.24) for MACE, 0.88 (0.74-1.04) for heart failure, and 0.60 (0.47-0.77) for serious renal events. In secondary outcome analyses, use of SGLT2 inhibitors versus GLP-1 receptor agonists was not associated with statistically significant differences for the risk of myocardial infarction (HR 1.09 [95% CI 1.00-1.19]), cardiovascular death (HR 0.97 [95% CI 0.84-1.12]), death from renal causes (HR 0.75 [95% CI 0.41-1.35]), or any cause death (HR 1.01 [95% CI 0.94-1.09]), while the risk of stroke was higher (HR 1.14 [95% CI 1.03-1.26]), and the risk of renal replacement therapy (HR 0.74 [95% CI 0.56-0.97]) and hospitalization for renal events (HR 0.75 [95% CI 0.65-0.88]) were lower among users of SGLT2 inhibitors. Conclusions: Use of SGLT2 inhibitors versus GLP-1 receptor agonists was associated with a similar risk of heart failure and a lower risk of serious renal events, while use of GLP-1 receptor agonists versus SGLT2 inhibitors was associated with a slightly lower risk of MACE. In as-treated analyses, the associations with MACE and serious renal events increased in magnitude, and the HR for heart failure tended towards a protective association for SGLT2 inhibitors.

KW - antidiabetic drug

KW - cardiovascular disease

KW - cohort study

KW - dapagliflozin

KW - GLP-1 analogue

KW - pharmaco-epidemiology

U2 - 10.1111/dom.14598

DO - 10.1111/dom.14598

M3 - Journal article

C2 - 34738703

AN - SCOPUS:85119699273

VL - 24

SP - 473

EP - 485

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

SN - 1462-8902

IS - 3

ER -