A Nationwide Danish Comparative Effectiveness Study of GLP-1 RA, SGLT2i and DPP-4i Treatment on Risk of Stroke, Myocardial Infarction and Mortality in Type 2 Diabetes

Sidsel Hastrup; Jakob N Hedegaard; Grethe Andersen; Merete Osler; Jørgen Rungby; Søren Paaske Johnsen

doi:10.1002/edm2.70165

A Nationwide Danish Comparative Effectiveness Study of GLP-1 RA, SGLT2i and DPP-4i Treatment on Risk of Stroke, Myocardial Infarction and Mortality in Type 2 Diabetes

Sidsel Hastrup^*, Jakob N Hedegaard, Grethe Andersen, Merete Osler, Jørgen Rungby, Søren Paaske Johnsen

^*Corresponding author af dette arbejde

Abstract

AIMS: Cardiovascular outcome trials have demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce the risk of major adverse cardiovascular events, whereas dipeptidyl peptidase-4 inhibitors (DPP-4i) have not shown cardiovascular benefits. We aimed to compare the effectiveness in routine clinical settings of incident use of either GLP-1 RA, SGLT2i or DPP-4i among type 2 diabetes on the stroke risk and as secondary outcomes myocardial infarction and all-cause mortality.

METHODS: A nationwide population-based cohort study consisted of persons with type 2 diabetes who were new users of a GLP-1 RA, SGLT2i or DPP-4i and without prior stroke from 2014 to 2020 in Denmark using an active comparator design. They were followed from initiation of medication up to a maximum of 2 years for incident outcomes. Estimates were adjusted for age, sex, calendar year of initiation, socio-economic factors, medication and co-morbidity.

RESULTS: The study included 19,999 new users of a GLP-1 RA; 24,702 of a SGLT2i and 41,943 of a DPP-4i. The new users of GLP-1 RA had a lower incidence of stroke when compared to new users of DPP-4i, adjusted hazard rate ratios (aHRR): 0.69 95% confidence interval (0.53-0.91). There was no significant difference in stroke incidence between the new users of SGLT2i versus DPP4-4i and SGLT2i versus GLP-1 RA: aHRR 0.80 (0.64-1.01) and 1.17 (0.87-1.57). The new users of GLP-1 RA and SGLT2i had lower risk of mortality in comparison with new users of DPP-4i. The risk of myocardial infarction was not significantly different between the compared groups.

CONCLUSIONS: New users of GLP-1 RA with type 2 diabetes had a lower risk of first stroke and new users of GLP-1 RA and SGLT2i had lower mortality. These data could help guide the choice of glucose-lowering medications in persons with type 2 diabetes.

Originalsprog	Engelsk
Artikelnummer	e70165
Tidsskrift	Endocrinology, Diabetes & Metabolism
Vol/bind	9
Udgave nummer	1
Sider (fra-til)	e70165
ISSN	2398-9238
DOI	https://doi.org/10.1002/edm2.70165
Status	Udgivet - jan. 2026

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10.1002/edm2.70165Licens: CC BY

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A Nationwide Danish Comparative Effectiveness Study of GLP-1 RA, SGLT2i and DPP-4i Treatment on Risk of Stroke, Myocardial Infarction and Mortality in Type 2 Diabetes. / Hastrup, Sidsel; Hedegaard, Jakob N; Andersen, Grethe et al.
I: Endocrinology, Diabetes & Metabolism, Bind 9, Nr. 1, e70165, 01.2026, s. e70165.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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title = "A Nationwide Danish Comparative Effectiveness Study of GLP-1 RA, SGLT2i and DPP-4i Treatment on Risk of Stroke, Myocardial Infarction and Mortality in Type 2 Diabetes",

abstract = "AIMS: Cardiovascular outcome trials have demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce the risk of major adverse cardiovascular events, whereas dipeptidyl peptidase-4 inhibitors (DPP-4i) have not shown cardiovascular benefits. We aimed to compare the effectiveness in routine clinical settings of incident use of either GLP-1 RA, SGLT2i or DPP-4i among type 2 diabetes on the stroke risk and as secondary outcomes myocardial infarction and all-cause mortality.METHODS: A nationwide population-based cohort study consisted of persons with type 2 diabetes who were new users of a GLP-1 RA, SGLT2i or DPP-4i and without prior stroke from 2014 to 2020 in Denmark using an active comparator design. They were followed from initiation of medication up to a maximum of 2 years for incident outcomes. Estimates were adjusted for age, sex, calendar year of initiation, socio-economic factors, medication and co-morbidity.RESULTS: The study included 19,999 new users of a GLP-1 RA; 24,702 of a SGLT2i and 41,943 of a DPP-4i. The new users of GLP-1 RA had a lower incidence of stroke when compared to new users of DPP-4i, adjusted hazard rate ratios (aHRR): 0.69 95% confidence interval (0.53-0.91). There was no significant difference in stroke incidence between the new users of SGLT2i versus DPP4-4i and SGLT2i versus GLP-1 RA: aHRR 0.80 (0.64-1.01) and 1.17 (0.87-1.57). The new users of GLP-1 RA and SGLT2i had lower risk of mortality in comparison with new users of DPP-4i. The risk of myocardial infarction was not significantly different between the compared groups.CONCLUSIONS: New users of GLP-1 RA with type 2 diabetes had a lower risk of first stroke and new users of GLP-1 RA and SGLT2i had lower mortality. These data could help guide the choice of glucose-lowering medications in persons with type 2 diabetes.",

keywords = "Humans, Diabetes Mellitus, Type 2/drug therapy, Sodium-Glucose Transporter 2 Inhibitors/therapeutic use, Denmark/epidemiology, Male, Female, Stroke/epidemiology, Dipeptidyl-Peptidase IV Inhibitors/therapeutic use, Middle Aged, Aged, Myocardial Infarction/epidemiology, Glucagon-Like Peptide-1 Receptor Agonists, Hypoglycemic Agents/therapeutic use, Cohort Studies, Risk Factors",

author = "Sidsel Hastrup and Hedegaard, {Jakob N} and Grethe Andersen and Merete Osler and J{\o}rgen Rungby and Johnsen, {S{\o}ren Paaske}",

note = "{\textcopyright} 2026 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.",

year = "2026",

month = jan,

doi = "10.1002/edm2.70165",

language = "English",

volume = "9",

pages = "e70165",

journal = "Endocrinology, Diabetes & Metabolism",

issn = "2398-9238",

publisher = "John/Wiley & Sons, Inc. John/Wiley & Sons Ltd",

number = "1",

}

TY - JOUR

T1 - A Nationwide Danish Comparative Effectiveness Study of GLP-1 RA, SGLT2i and DPP-4i Treatment on Risk of Stroke, Myocardial Infarction and Mortality in Type 2 Diabetes

AU - Hastrup, Sidsel

AU - Hedegaard, Jakob N

AU - Andersen, Grethe

AU - Osler, Merete

AU - Rungby, Jørgen

AU - Johnsen, Søren Paaske

PY - 2026/1

Y1 - 2026/1

N2 - AIMS: Cardiovascular outcome trials have demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce the risk of major adverse cardiovascular events, whereas dipeptidyl peptidase-4 inhibitors (DPP-4i) have not shown cardiovascular benefits. We aimed to compare the effectiveness in routine clinical settings of incident use of either GLP-1 RA, SGLT2i or DPP-4i among type 2 diabetes on the stroke risk and as secondary outcomes myocardial infarction and all-cause mortality.METHODS: A nationwide population-based cohort study consisted of persons with type 2 diabetes who were new users of a GLP-1 RA, SGLT2i or DPP-4i and without prior stroke from 2014 to 2020 in Denmark using an active comparator design. They were followed from initiation of medication up to a maximum of 2 years for incident outcomes. Estimates were adjusted for age, sex, calendar year of initiation, socio-economic factors, medication and co-morbidity.RESULTS: The study included 19,999 new users of a GLP-1 RA; 24,702 of a SGLT2i and 41,943 of a DPP-4i. The new users of GLP-1 RA had a lower incidence of stroke when compared to new users of DPP-4i, adjusted hazard rate ratios (aHRR): 0.69 95% confidence interval (0.53-0.91). There was no significant difference in stroke incidence between the new users of SGLT2i versus DPP4-4i and SGLT2i versus GLP-1 RA: aHRR 0.80 (0.64-1.01) and 1.17 (0.87-1.57). The new users of GLP-1 RA and SGLT2i had lower risk of mortality in comparison with new users of DPP-4i. The risk of myocardial infarction was not significantly different between the compared groups.CONCLUSIONS: New users of GLP-1 RA with type 2 diabetes had a lower risk of first stroke and new users of GLP-1 RA and SGLT2i had lower mortality. These data could help guide the choice of glucose-lowering medications in persons with type 2 diabetes.

AB - AIMS: Cardiovascular outcome trials have demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce the risk of major adverse cardiovascular events, whereas dipeptidyl peptidase-4 inhibitors (DPP-4i) have not shown cardiovascular benefits. We aimed to compare the effectiveness in routine clinical settings of incident use of either GLP-1 RA, SGLT2i or DPP-4i among type 2 diabetes on the stroke risk and as secondary outcomes myocardial infarction and all-cause mortality.METHODS: A nationwide population-based cohort study consisted of persons with type 2 diabetes who were new users of a GLP-1 RA, SGLT2i or DPP-4i and without prior stroke from 2014 to 2020 in Denmark using an active comparator design. They were followed from initiation of medication up to a maximum of 2 years for incident outcomes. Estimates were adjusted for age, sex, calendar year of initiation, socio-economic factors, medication and co-morbidity.RESULTS: The study included 19,999 new users of a GLP-1 RA; 24,702 of a SGLT2i and 41,943 of a DPP-4i. The new users of GLP-1 RA had a lower incidence of stroke when compared to new users of DPP-4i, adjusted hazard rate ratios (aHRR): 0.69 95% confidence interval (0.53-0.91). There was no significant difference in stroke incidence between the new users of SGLT2i versus DPP4-4i and SGLT2i versus GLP-1 RA: aHRR 0.80 (0.64-1.01) and 1.17 (0.87-1.57). The new users of GLP-1 RA and SGLT2i had lower risk of mortality in comparison with new users of DPP-4i. The risk of myocardial infarction was not significantly different between the compared groups.CONCLUSIONS: New users of GLP-1 RA with type 2 diabetes had a lower risk of first stroke and new users of GLP-1 RA and SGLT2i had lower mortality. These data could help guide the choice of glucose-lowering medications in persons with type 2 diabetes.

KW - Humans

KW - Diabetes Mellitus, Type 2/drug therapy

KW - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use

KW - Denmark/epidemiology

KW - Male

KW - Female

KW - Stroke/epidemiology

KW - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use

KW - Middle Aged

KW - Aged

KW - Myocardial Infarction/epidemiology

KW - Glucagon-Like Peptide-1 Receptor Agonists

KW - Hypoglycemic Agents/therapeutic use

KW - Cohort Studies

KW - Risk Factors

U2 - 10.1002/edm2.70165

DO - 10.1002/edm2.70165

M3 - Journal article

C2 - 41578841

SN - 2398-9238

VL - 9

SP - e70165

JO - Endocrinology, Diabetes & Metabolism

JF - Endocrinology, Diabetes & Metabolism

IS - 1

M1 - e70165

ER -

A Nationwide Danish Comparative Effectiveness Study of GLP-1 RA, SGLT2i and DPP-4i Treatment on Risk of Stroke, Myocardial Infarction and Mortality in Type 2 Diabetes

Abstract

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