Glucagonlike peptide-1 receptor agonists versus dipeptidyl peptidase-4 inhibitors in ischemic strokes with diabetes 2.
Open accessAbstract
Background and purpose: Cardiovascular outcome trials demonstrate that glucagonlike peptide‐1 receptor agonists (GLP‐1RAs) reduce the risk of major adverse cardiovascular events in patients with type 2 diabetes (T2D), whereas dipeptidyl peptidase‐4 inhibitors (DPP‐4is) have not shown cardiovascular benefits. We compared acute ischemic stroke (AIS) with T2D treated with either a GLP‐1RA or DPP‐4i prior to the index stroke. Methods: This national cohort study included AIS patients with T2D from 2017 to 2020 in Denmark who were users of a GLP‐1RA or DPP‐4i. To be categorized as a user, we required at least 12 months of exposure and no concurrent treatment with another newer glucose‐lowering medication during the last 3 months prior to the index stroke. GLP‐1RA users were compared to users of DPP‐4i while adjusting for the calendar year of index stroke, age, sex, comorbidity, and socioeconomic factors. Results: The study included 1567 AIS events with T2D; 593 were users of GLP‐1RA and 974 of DPP‐4i. The absolute risk of a very severe stroke was 2.4% (95% confidence interval [CI] = 1.2–3.7) in GLP‐1RA users and 6.1% (95% CI = 4.6–7.7) in DPP‐4i users. The corresponding adjusted risk ratio (aRR) of GLP‐1RA versus DPP‐4i was 0.49 (95% CI = 0.24–1.00). The aRRs of 30‐day and 365‐day mortality were 0.55 (95% CI = 0.32–0.94) and 0.72 (95% CI = 0.53–0.98), respectively. Conclusions: The risk of a very severe stroke as well as the 30‐day and 365‐day poststroke mortality rates were lower among the AIS patients with comorbid T2D receiving GLP‐1RA prior to the index stroke compared to those receiving DPP‐4i. Hence, GLP‐1RA may improve stroke outcomes in comparison with DPP‐4i.
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A Danish study comparing GLP-1RAs and DPP-4 inhibitors in patients with type 2 diabetes found that GLP-1RA users had a lower risk of severe stroke (adjusted risk ratio, 0.49; 95% CI, 0.24-1.00) and reduced mortality.
“Similarly, another Danish study comparing GLP-1RAs and dipeptidyl peptidase 4 (DPP-4) inhibitors in patients with type 2 diabetes found that GLP-1RA users had a lower risk of severe stroke (adjusted risk ratio, 0.49; 95% CI, 0.24-1.00)and reduced mortality.38”
From Neurodegeneration and Stroke After Semaglutide and Tirzepatide in Patients With Diabetes and Obesity (2025) · cites this paper as [38]
The Results (Table 2) report the cited adjusted risk ratio of 0.49 (95% CI, 0.24–1.00) and lower 30- and 365-day mortality among GLP-1RA users. The measured stroke outcome was specifically a “very severe stroke” among patients with acute ischemic stroke and type 2 diabetes, rather than severe stroke more generally. (LLM, conf=0.85)
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Cites
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Neurodegeneration and Stroke After Semaglutide and Tirzepatide in Patients With Diabetes and Obesity
Lin, H.-T., Tsai, Y.-F., Liao, P.-L., & Wei, J. C.-C. (2025) · JAMA Network Open · doi:10.1001/jamanetworkopen.2025.21016 · Cited by 43 · see citing works
- Authors
- Hastrup, S., Hedegaard, J. N., Andersen, G., Rungby, J., & Johnsen, S. P.
- Affiliations
- Aarhus University Hospital (DK)
- Aalborg University (DK)
- Aarhus University (DK)
- Bispebjerg Hospital (DK)
- Danish Centre for Health Services Research, Department of Clinical Medicine Aalborg University Aalborg Denmark
- Corresponding author
- Hastrup, Sidsel
- Venue
- European Journal of Neurology
- Publisher
- Wiley
- Published
- 2024-05-07
- Volume
- 31
- Issue
- 8
- Pages
- e16329-e16329
- ISSN
- 1351-5101 (ISSN-L)
- 1468-1331
- PMC
- PMC11235957
- OpenAlex
- W4396740585
- Cited by
- 6
- References
- 7
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1
- FWCI
- 1.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- European Journal of Neurology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- VBN Forskningsportal (Aalborg Universitet) (submittedVersion, cc-by-nc-nd)
- Funders
- Novo Nordisk
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- GLP-1 receptor agonists, DPP-4 inhibitors, acute ischemic stroke, type 2 diabetes, post-stroke mortality, glucose-lowering medications, stroke outcome, antidiabetic drug comparison, cardiovascular risk reduction, socioeconomic factors, comorbidities
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Ischemic Stroke, Glucagon-Like Peptide-1 Receptor Agonists, Aged, Aged, 80 and over, Denmark, Diabetes Mellitus, Type 2, Female, Humans, Hypoglycemic Agents, Male, Middle Aged, Cohort Studies, Dipeptidyl-Peptidase IV Inhibitors
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