All-cause mortality and cardiovascular outcomes with sodium-glucose Co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists and with combination therapy in people with type 2 diabetes

David R. Riley; Hani Essa; Philip Austin; Frank Preston; Isatu Kargbo; Gema Hernández Ibarburu; Ramandeep Ghuman; Daniel J. Cuthbertson; Gregory Y. H. Lip; Uazman Alam

doi:10.1111/dom.15185

All-cause mortality and cardiovascular outcomes with sodium-glucose Co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists and with combination therapy in people with type 2 diabetes

David R. Riley^*, Hani Essa, Philip Austin, Frank Preston, Isatu Kargbo, Gema Hernández Ibarburu, Ramandeep Ghuman, Daniel J. Cuthbertson, Gregory Y. H. Lip, Uazman Alam

^*Corresponding author for this work

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Abstract

AIM: To assess the relationship of sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor analogues (GLP-1RA) and their combination (SGLT2i + GLP-1RA) with 5-year risk of all-cause mortality, hospitalization and cardiovascular/macrovascular disease in people with type 2 diabetes.

MATERIALS AND METHODS: Retrospective cohort analysis of 2.2 million people with type 2 diabetes receiving insulin across 85 health care organizations using a global federated health research network. Three intervention cohorts (SGLT2i, GLP-1RA and SGLT2i + GLP-1RA) were compared against a control cohort (no SGLT2i/GLP-1RA). Propensity score matching for age, ischaemic heart disease, sex, hypertension, chronic kidney disease, heart failure and glycated haemoglobin was used to balance cohorts 1:1 (SGLT2i, n = 143 600; GLP-1RA, n = 186 841; SGLT-2i + GLP-1RA, n = 108 504). A sub-analysis comparing combination and monotherapy cohorts was also performed.

RESULTS: The intervention cohorts showed a reduced hazard ratio (HR, 95% confidence interval) over 5 years compared with the control cohort for all-cause mortality (SGLT2i 0.49, 0.48-0.50; GLP-1RA 0.47, 0.46-0.48; combination 0.25, 0.24-0.26), hospitalization (0.73, 0.72-0.74; 0.69, 0.68-0.69; 0.60, 0.59-0.61) and acute myocardial infarct (0.75, 0.72-0.78; 0.70, 0.68-0.73; 0.63, 0.60-0.66), respectively. All other outcomes showed a significant risk reduction in favour of the intervention cohorts. The sub-analysis showed a significant risk reduction in all-cause mortality for combination therapy versus SGLT2i (0.53, 0.50-0.55) and GLP-1RA (0.56, 0.54-0.59).

CONCLUSIONS: SGLT2i, GLP-1RAs or combination therapy confers mortality and cardiovascular protection in people with type 2 diabetes over 5 years. Combination therapy was associated with the greatest risk reduction in all-cause mortality versus a propensity matched control cohort. In addition, combination therapy offers a reduction in 5-year all-cause mortality when compared directly against either monotherapy.

Original language	English
Journal	Diabetes, Obesity and Metabolism
Volume	25
Issue number	10
Pages (from-to)	2897-2909
Number of pages	13
ISSN	1462-8902
DOIs	https://doi.org/10.1111/dom.15185
Publication status	Published - Oct 2023

Bibliographical note

Keywords

cardiovascular disease
chronic kidney disease
glucagon-like peptide-1 receptor agonists
hospitalization
mortality
sodium-glucose cotransporter 2 inhibitors
type 2 diabetes

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Riley, D. R., Essa, H., Austin, P., Preston, F., Kargbo, I., Ibarburu, G. H., Ghuman, R., Cuthbertson, D. J., Lip, G. Y. H., & Alam, U. (2023). All-cause mortality and cardiovascular outcomes with sodium-glucose Co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists and with combination therapy in people with type 2 diabetes. Diabetes, Obesity and Metabolism, 25(10), 2897-2909. https://doi.org/10.1111/dom.15185

@article{cf820eead639415b842e65309c57deb6,

title = "All-cause mortality and cardiovascular outcomes with sodium-glucose Co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists and with combination therapy in people with type 2 diabetes",

abstract = "AIM: To assess the relationship of sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor analogues (GLP-1RA) and their combination (SGLT2i + GLP-1RA) with 5-year risk of all-cause mortality, hospitalization and cardiovascular/macrovascular disease in people with type 2 diabetes.MATERIALS AND METHODS: Retrospective cohort analysis of 2.2 million people with type 2 diabetes receiving insulin across 85 health care organizations using a global federated health research network. Three intervention cohorts (SGLT2i, GLP-1RA and SGLT2i + GLP-1RA) were compared against a control cohort (no SGLT2i/GLP-1RA). Propensity score matching for age, ischaemic heart disease, sex, hypertension, chronic kidney disease, heart failure and glycated haemoglobin was used to balance cohorts 1:1 (SGLT2i, n = 143 600; GLP-1RA, n = 186 841; SGLT-2i + GLP-1RA, n = 108 504). A sub-analysis comparing combination and monotherapy cohorts was also performed.RESULTS: The intervention cohorts showed a reduced hazard ratio (HR, 95% confidence interval) over 5 years compared with the control cohort for all-cause mortality (SGLT2i 0.49, 0.48-0.50; GLP-1RA 0.47, 0.46-0.48; combination 0.25, 0.24-0.26), hospitalization (0.73, 0.72-0.74; 0.69, 0.68-0.69; 0.60, 0.59-0.61) and acute myocardial infarct (0.75, 0.72-0.78; 0.70, 0.68-0.73; 0.63, 0.60-0.66), respectively. All other outcomes showed a significant risk reduction in favour of the intervention cohorts. The sub-analysis showed a significant risk reduction in all-cause mortality for combination therapy versus SGLT2i (0.53, 0.50-0.55) and GLP-1RA (0.56, 0.54-0.59).CONCLUSIONS: SGLT2i, GLP-1RAs or combination therapy confers mortality and cardiovascular protection in people with type 2 diabetes over 5 years. Combination therapy was associated with the greatest risk reduction in all-cause mortality versus a propensity matched control cohort. In addition, combination therapy offers a reduction in 5-year all-cause mortality when compared directly against either monotherapy.",

keywords = "cardiovascular disease, chronic kidney disease, glucagon-like peptide-1 receptor agonists, hospitalization, mortality, sodium-glucose cotransporter 2 inhibitors, type 2 diabetes",

author = "Riley, {David R.} and Hani Essa and Philip Austin and Frank Preston and Isatu Kargbo and Ibarburu, {Gema Hern{\'a}ndez} and Ramandeep Ghuman and Cuthbertson, {Daniel J.} and Lip, {Gregory Y. H.} and Uazman Alam",

note = "{\textcopyright} 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.",

year = "2023",

month = oct,

doi = "10.1111/dom.15185",

language = "English",

volume = "25",

pages = "2897--2909",

journal = "Diabetes, Obesity and Metabolism",

issn = "1462-8902",

publisher = "Wiley-Blackwell",

number = "10",

}

Riley, DR, Essa, H, Austin, P, Preston, F, Kargbo, I, Ibarburu, GH, Ghuman, R, Cuthbertson, DJ, Lip, GYH & Alam, U 2023, 'All-cause mortality and cardiovascular outcomes with sodium-glucose Co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists and with combination therapy in people with type 2 diabetes', Diabetes, Obesity and Metabolism, vol. 25, no. 10, pp. 2897-2909. https://doi.org/10.1111/dom.15185

All-cause mortality and cardiovascular outcomes with sodium-glucose Co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists and with combination therapy in people with type 2 diabetes. / Riley, David R.; Essa, Hani; Austin, Philip et al.
In: Diabetes, Obesity and Metabolism, Vol. 25, No. 10, 10.2023, p. 2897-2909.

Research output: Contribution to journal › Journal article › Research › peer-review

TY - JOUR

T1 - All-cause mortality and cardiovascular outcomes with sodium-glucose Co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists and with combination therapy in people with type 2 diabetes

AU - Riley, David R.

AU - Essa, Hani

AU - Austin, Philip

AU - Preston, Frank

AU - Kargbo, Isatu

AU - Ibarburu, Gema Hernández

AU - Ghuman, Ramandeep

AU - Cuthbertson, Daniel J.

AU - Lip, Gregory Y. H.

AU - Alam, Uazman

PY - 2023/10

Y1 - 2023/10

N2 - AIM: To assess the relationship of sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor analogues (GLP-1RA) and their combination (SGLT2i + GLP-1RA) with 5-year risk of all-cause mortality, hospitalization and cardiovascular/macrovascular disease in people with type 2 diabetes.MATERIALS AND METHODS: Retrospective cohort analysis of 2.2 million people with type 2 diabetes receiving insulin across 85 health care organizations using a global federated health research network. Three intervention cohorts (SGLT2i, GLP-1RA and SGLT2i + GLP-1RA) were compared against a control cohort (no SGLT2i/GLP-1RA). Propensity score matching for age, ischaemic heart disease, sex, hypertension, chronic kidney disease, heart failure and glycated haemoglobin was used to balance cohorts 1:1 (SGLT2i, n = 143 600; GLP-1RA, n = 186 841; SGLT-2i + GLP-1RA, n = 108 504). A sub-analysis comparing combination and monotherapy cohorts was also performed.RESULTS: The intervention cohorts showed a reduced hazard ratio (HR, 95% confidence interval) over 5 years compared with the control cohort for all-cause mortality (SGLT2i 0.49, 0.48-0.50; GLP-1RA 0.47, 0.46-0.48; combination 0.25, 0.24-0.26), hospitalization (0.73, 0.72-0.74; 0.69, 0.68-0.69; 0.60, 0.59-0.61) and acute myocardial infarct (0.75, 0.72-0.78; 0.70, 0.68-0.73; 0.63, 0.60-0.66), respectively. All other outcomes showed a significant risk reduction in favour of the intervention cohorts. The sub-analysis showed a significant risk reduction in all-cause mortality for combination therapy versus SGLT2i (0.53, 0.50-0.55) and GLP-1RA (0.56, 0.54-0.59).CONCLUSIONS: SGLT2i, GLP-1RAs or combination therapy confers mortality and cardiovascular protection in people with type 2 diabetes over 5 years. Combination therapy was associated with the greatest risk reduction in all-cause mortality versus a propensity matched control cohort. In addition, combination therapy offers a reduction in 5-year all-cause mortality when compared directly against either monotherapy.

AB - AIM: To assess the relationship of sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor analogues (GLP-1RA) and their combination (SGLT2i + GLP-1RA) with 5-year risk of all-cause mortality, hospitalization and cardiovascular/macrovascular disease in people with type 2 diabetes.MATERIALS AND METHODS: Retrospective cohort analysis of 2.2 million people with type 2 diabetes receiving insulin across 85 health care organizations using a global federated health research network. Three intervention cohorts (SGLT2i, GLP-1RA and SGLT2i + GLP-1RA) were compared against a control cohort (no SGLT2i/GLP-1RA). Propensity score matching for age, ischaemic heart disease, sex, hypertension, chronic kidney disease, heart failure and glycated haemoglobin was used to balance cohorts 1:1 (SGLT2i, n = 143 600; GLP-1RA, n = 186 841; SGLT-2i + GLP-1RA, n = 108 504). A sub-analysis comparing combination and monotherapy cohorts was also performed.RESULTS: The intervention cohorts showed a reduced hazard ratio (HR, 95% confidence interval) over 5 years compared with the control cohort for all-cause mortality (SGLT2i 0.49, 0.48-0.50; GLP-1RA 0.47, 0.46-0.48; combination 0.25, 0.24-0.26), hospitalization (0.73, 0.72-0.74; 0.69, 0.68-0.69; 0.60, 0.59-0.61) and acute myocardial infarct (0.75, 0.72-0.78; 0.70, 0.68-0.73; 0.63, 0.60-0.66), respectively. All other outcomes showed a significant risk reduction in favour of the intervention cohorts. The sub-analysis showed a significant risk reduction in all-cause mortality for combination therapy versus SGLT2i (0.53, 0.50-0.55) and GLP-1RA (0.56, 0.54-0.59).CONCLUSIONS: SGLT2i, GLP-1RAs or combination therapy confers mortality and cardiovascular protection in people with type 2 diabetes over 5 years. Combination therapy was associated with the greatest risk reduction in all-cause mortality versus a propensity matched control cohort. In addition, combination therapy offers a reduction in 5-year all-cause mortality when compared directly against either monotherapy.

KW - cardiovascular disease

KW - chronic kidney disease

KW - glucagon-like peptide-1 receptor agonists

KW - hospitalization

KW - mortality

KW - sodium-glucose cotransporter 2 inhibitors

KW - type 2 diabetes

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U2 - 10.1111/dom.15185

DO - 10.1111/dom.15185

M3 - Journal article

C2 - 37385958

SN - 1462-8902

VL - 25

SP - 2897

EP - 2909

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

IS - 10

ER -

All-cause mortality and cardiovascular outcomes with sodium-glucose Co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists and with combination therapy in people with type 2 diabetes

Abstract

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