The impact of novel antidiabetic agents on stroke, MI, and mortality in T2D patients: a nationwide cohort study


Type 2 diabetes (T2D) increases the risk of ischemic and hemorrhagic stroke to over 50%.1 If a stroke occurs in these patients, the prognosis is severe in terms of higher risk of recurrent stroke, mortality, hospital admissions, and adverse cognitive outcomes.1 Hence, there exists a need to prevent the occurrence of an initial stroke, particularly in T2D patients.1 At the EASD Annual Meeting 2023, Dr. Sidsel Hastrup presented the results of a nationwide population-based study conducted in Denmark, which compared the effectiveness of glucagon-like peptide-1 receptor agonist (GLP-1RA), sodium-glucose cotransporter-2 inhibitor (SGLT2i), or dipeptidyl peptidase-4 inhibitor (DPP-4i) on T2D-related outcomes.

The cohort study was conducted with data from the national registries in Denmark to investigate the risk of stroke and other outcomes in T2D patients.1 This study recruited patients with T2D without a history of stroke and were new users of GLP-1RA, SGLT2i, or DPP-4i between 2014 and 2020.1 A total of 19,999 GLP-1RA users, 24,702 SGLT2i users, and 41,943 DPP-4i users were included in this study.1

The primary endpoint was the incidence of stroke, and secondary endpoints included all-cause mortality and the incidence of myocardial infarction (MI).1 To account for the differences between the groups, the data were adjusted for age, gender, year of initiation, socio-economic factors, and other comorbidities.1 GLP-1RA and SGLT2i can potentially lower the risk of stroke and all-cause mortality, while GLP-1RA and SGLT2i can lower the risk of MI in new users with T2D without a history of stroke.1 GLP-1RA appeared to be the most beneficial due to its benefits on several cardiovascular and mortality outcomes.1


Primary endpoint:

  • The primary endpoint was the incidence of stroke1
  • Compared with patients receiving DPP-4i, the risk of stroke was lower in patients receiving GLP-1RA [adjusted hazard ratio (aHR)=0.73; 95% CI: 0.56-0.96] and SGLT2i (aHR=0.77; 95% CI: 0.61-0.97) respectively1
  • When comparing between patients who received GLP-1RA or SGLT2i, a similar risk of stroke was observed (aHR=1.02; 95% CI: 0.77-1.37)1

Secondary endpoints: 

  • The secondary endpoints included all-cause mortality and the incidence of MI1
  • The rates of all-cause mortality were similarly lower by 54% in GLP-1RA users (aHR=0.46; 95% CI: 0.38-0.57) and 61% in SGLT2i users (aHR=0.39; 95% CI: 0.33-0.46) compared with DPP-4i1
  • All-cause mortality was also slightly lower in SGLT2i users compared with DPP-4i users [aHR=0.91 (95% CI: 0.72-1.16)]1
  • However, the rates of MI were marginally higher with GLP1-RA (aHR=1.02; 95% CI: 0.77-1.34) and SGLT2i (aHR=1.27; 95% CI: 1.01-1.59) respectively when compared with patients receiving DPP-4i1
  • Rates of MI were higher in SGLT2i users compared with DPP-4i users with an aHR of 1.32 (95% CI: 1.01-1.72)1


"GLP-1RA seems to be the best choice to protect against both stroke and MI. Wider use of GLP-1RA and SGLT2i may be beneficial in terms of preventing stroke and mortality in T2D"

Dr. Sidsel Hastrup
Danish Stroke Center,
Department of Neurology, Aarhus University Hospital,
Aarhus, Denmark

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