Patients with type 2 diabetes and obesity treated with semaglutide or tirzepatide had lower risks of stroke and death, and reduced dementia risk driven by other subtypes, according to a recent cohort study.
Researchers evaluated the association of semaglutide and tirzepatide with neurodegenerative and cerebrovascular outcomes in patients with type 2 diabetes (T2D) and obesity. The researchers used electronic health record data from the TriNetX U.S. collaborative network to assess the incidence of dementia, stroke, and all-cause mortality in patients initiating glucagon-like peptide 1 receptor agonists (GLP-1 RAs) compared with those starting other antidiabetic medications.
The analysis included 60,860 adults aged 40 years or older, evenly divided into GLP-1 RA and comparator groups following 1:1 propensity score matching. Patients had no prior neurodegenerative or cerebrovascular diagnoses and received at least 1 year of follow-up.
Patients exposed to semaglutide or tirzepatide were compared with patients who received treatment using biguanides, sulfonylureas, thiazolidinediones, α-glucosidase inhibitors, sodium-glucose cotransporter 2 inhibitors, and dipeptidyl peptidase 4 inhibitors. Cox proportional hazards models and Kaplan-Meier estimates were used to evaluate outcomes.
Over a mean follow-up of 1.77 years, GLP-1RA users had lower risks of dementia (hazard ratio [HR], 0.63), ischemic stroke (HR, 0.81), and all-cause mortality (HR, 0.7) compared with users of other antidiabetic agents. The risks of Parkinson disease (HR, 0.96) and intracerebral hemorrhage (HR, 0.82) did not differ significantly between groups. Subgroup analyses showed more pronounced benefits in patients aged 60 years or older (HR, 0.85), women (HR, 0.85), and those with a body mass index between 30 and 40 (HR, 0.82).
In further analyses, semaglutide was associated with a reduced risk of dementia (HR, 0.63), while tirzepatide was associated with decreased risk of stroke (HR, 0.69) and all-cause mortality (HR, 0.48).
The findings suggest that these GLP-1RAs may provide neuroprotective and survival advantages in patients with T2D and obesity, supporting their role in addressing long-term cognitive and cerebrovascular risks beyond glycemic control.
The authors reported no conflicts of interest.
Source: JAMA Network