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Semaglutide and tirzepatide lower risk for dementia, stroke, and all-cause mortality among patients with type 2 diabetes (T2D) and comorbid obesity, according to findings published in JAMA Network Open.
In 2024, both diabetes and obesity were identified as modifiable risk factors for dementia and associated with elevated risk for neurodegenerative and cerebrovascular diseases.
To assess whether glucagon-like peptide 1 receptor agonists (GLP-1RAs) mitigate risk for neurological and cerebrovascular outcomes, investigators from Chang Gung Memorial Hospital at Linkou and China Medical University in Taiwan sourced data from the TriNetX network, which collected data from patients in the United States (US). Patients (N=290,606) aged 40 years and older with T2D and obesity who initiated semaglutide, tirzepatide, or other antidiabetic agents between 2017 and 2024 were evaluated for neurodegenerative and cerebrovascular diseases.
To balance for cohort differences, patients who initiated GLP-1RAs (n=30,430) were matched in a 1:1 ratio with those initiating other antidiabetic medications (n=30,430).
Among the pre-matched GLP-1RA (n=52,826) and other medication (n=161,945) recipients, who had mean (SD) ages of 57.2 (9.9) and 59.8 (10.8) years and BMI of 40.3 (7.6) and 38.4 (8.0) kg/m2, respectively, 54.1% and 47.5% were women, 56.2% and 56.7% were White, and 35.8% and 22.5% had glycated hemoglobin (HbA1c) of less than 7%, respectively.
Among the matched cohorts, the cumulative probabilities of receiving a neurodegenerative or cerebrovascular disease diagnosis among GLP-1RA and other medication users, respectively, were:
- 1.32% and 1.70% at 1 year;
- 3.46% and 4.16% at 3 years;
- 6.38% and 7.06% at 5 years; and,
- 7.19% and 9.96% at 7 years.
Overall, GLP-1RAs decreased risk for neurodegenerative and cerebrovascular diseases relative to other antidiabetic medications (hazard ratio [HR], 0.83; 95% CI, 0.75-0.93).
Stratified by specific diseases, GLP-1RA use was associated with reduced risk for dementia (HR, 0.63; 95% CI, 0.50-0.81) and ischemic stroke (HR, 0.81; 95% CI, 0.70-0.93), as well as all-cause mortality (HR, 0.70; 95% CI, 0.63-0.78).
Conversely, GLP-1RAs did not have a significant protective effect for Parkinson disease (HR, 0.96; 95% CI, 0.66-1.38), intracerebral hemorrhage (HR, 0.82; 95% CI, 0.62-1.08), or mild cognitive impairment (HR, 1.13; 95% CI, 0.87-1.46).
In the subgroup analyses, neurodegenerative and cerebrovascular disease risk decreased with GLP-1RA use among women (HR, 0.85; 95% CI, 0.74-0.97), patients aged 60 years and older (HR, 0.85; 95% CI, 0.74-0.99), White patients (HR, 0.86; 95% CI, 0.76-0.98), and patients with a BMI of 30 to 40 kg/m2 (HR, 0.82; 95% CI, 0.72-0.93).
In sensitivity analyses that used data from the Global TriNetX database or restricted the comparator group to new initiators of dipeptidyl peptidase 4 inhibitors, trends were consistent with the main analysis.
Study limitations include absence of data about frailty status or biomarker data.
The study authors concluded, “[W]e found electronic health record–based evidence that the use of GLP-1RAs, particularly semaglutide and tirzepatide, is associated with a lower incidence of dementia, stroke, and all-cause mortality in patients with both type 2 diabetes and obesity, suggesting potential neuroprotective and cerebrovascular benefits. These findings highlight the possible role of GLP-1RAs in mitigating neurodegenerative and cerebrovascular risks in this high-risk population.”
This article originally appeared on Endocrinology Advisor
