GLP-1RA, SGLT2i superior to DPP-4i at preventing stroke, death in T2D patients

Among type 2 diabetes (T2D) patients with and without comorbid cardiovascular disease, those who have been newly initiated to glucagon-like peptide-1 receptor agonists (GLP-1RA) or sodium-glucose cotransporter 2 inhibitors (SGLT2i) appear to enjoy greater reductions in the risks of stroke and death when compared with new users of dipeptidyl peptidase-4 inhibitors (DPP-4i), suggests a study.

“A wider use of GLP-1RA and SGLT2i may be beneficial in terms of preventing stroke and mortality,” said the researchers, led by Sidsel Hastrup from the Danish Stroke Center, Department of Neurology, Aarhus University Hospital, Aarhus, Denmark, who presented the results at EASD 2023.

Hastrup and colleagues conducted a nationwide population-based cohort study to examine the risk of stroke (ischaemic and haemorrhagic) among T2D patients in Denmark, who were new users of GLP-1RA, SGLT2i, and DPP-4i from 2014 and 2020, as well as to assess the risk of acute myocardial infarction (MI) and all-cause mortality.

Medical registries were accessed to obtain information on patients’ hospitalization history, drug use, and vital status. Those with prior stroke were excluded from the analysis.

The research team estimated hazard rate ratios (HRR) and risk ratios (RR) using Cox and Poisson regressions, respectively. They also applied inverse probability of treatment weight for the adjusted analyses. Adjustments were made for age, sex, year of initiation, migrant status, cohabitation status, income, education, diabetes duration, hypertension, atrial fibrillation, Charlson Comorbidity Index (CCI), and diabetes-related chronic complications.

Stroke, mortality benefits

Of the eligible patients, 23,474 were new users of GLP-1RA, 24,697 of SGLT2i, and 41,943 of DPP4-i. [EASD 2023, abstract 681]

New users of GLP-1RA (vs DPP-4i: adjusted HRR, 0.68, 95 percent confidence interval [CI], 0.53‒0.88) and SGLT2i (vs DPP-4i: adjusted HRR, 0.71, 95 percent CI, 0.5‒0.85) demonstrated a lower incidence of stroke relative to those of DPP-4i. In addition, no difference in stroke incidence was observed between new users of GLP-1RA and SGLT2i.

In terms of MI, the rates were similar between new users of GLP-1RA and DPP-4i, as were those between SGLT2i and DPP-4i. However, treatment with GLP-1RA (vs DPP-4i: adjusted HRR, 0.96, 95 percent CI, 0.74‒1.24) resulted in a much lower risk of MI when compared with SGLT2i (vs DPP-4i: adjusted HRR, 1.23, 95 percent CI, 0.99‒1.52).

Notably, the incidence of death within 365 days was also lower among new users of GLP-1RA (vs DPP-4i: RR, 0.31, 95 percent CI, 0.24‒0.39) and SGLT2i (vs DPP-4i: adjusted RR, 0.30, 95 percent CI, 0.25‒0.35) than those of DPP-4i.

“Cardiovascular outcome trials (CVOTs) demonstrate that GLP-1RA and SGLT2i reduce the risk of major adverse cardiovascular events in patients with T2D and cardiovascular disease (or at high risk), whereas DPP-4i have not shown cardiovascular benefits,” according to Hastrup and colleagues. “Two CVOTs using GLP-1RA also showed significant reduction in nonfatal stroke.”