# 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

## TL;DR

A study in Denmark found that GLP-1 RA medications lower stroke risk and both GLP-1 RA and SGLT2i reduce mortality in type 2 diabetes patients compared to DPP-4i.

## Contribution

This study provides real-world evidence comparing cardiovascular and mortality outcomes of three diabetes medications in a nationwide cohort.

## Key findings

- New users of GLP-1 RA had a 31% lower stroke risk compared to DPP-4i users.
- GLP-1 RA and SGLT2i users had lower mortality risk than DPP-4i users.
- No significant differences in myocardial infarction risk between the medication groups.

## Abstract

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.

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.

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.

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.

New users of GLP‐1 RA in type 2 diabetes had a lower risk of stroke and new users of GLP‐1 RA and SGLT2i in type 2 diabetes had a lower risk of mortality in comparison with new users of DPP‐4i in routine clinical settings. There were no differences in myocardial infarction.