Key result
GLP-1 RA use linked to ~31% lower stroke incidence versus DPP-4i.
Why the study?
GLP-1 RA and SGLT2i reduce MACE while DPP-4i have not shown cardiovascular benefits, but their comparative effectiveness in routine clinical settings on stroke risk and other outcomes needed evaluation.
Does incident use of GLP-1 RAs or SGLT2is reduce the risk of stroke, myocardial infarction, and mortality compared to DPP-4is in patients with type 2 diabetes without prior stroke?
Cohort (n=86,644)
Yes
Does incident use of GLP-1 RAs or SGLT2is reduce the risk of stroke, myocardial infarction, and mortality compared to DPP-4is in patients with type 2 diabetes without prior stroke?
In a nationwide real-world cohort of patients with type 2 diabetes, initiation of GLP-1 RAs was associated with a significantly lower risk of first stroke compared to DPP-4 inhibitors, and both GLP-1 RAs and SGLT2is were associated with lower all-cause mortality.
GLP-1 RA initiation was associated with lower first-stroke risk versus DPP-4i in T2D; extends observational data but leaves open causal confirmation before practice change.
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.
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Hastrup et al. (2026) conducted a cohort in Type 2 diabetes (n=86,644). GLP-1 RA vs. DPP-4i was evaluated on Incident stroke (aHRR 0.69, 95% CI 0.53-0.91). New use of GLP-1 RA in patients with type 2 diabetes was associated with a lower risk of incident stroke compared to DPP-4i (aHRR 0.69; 95% CI 0.53-0.91).
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