Long-Term Risk of Cognitive Impairment with GLP-1 Analogues in Older Adults with Type 2 Diabetes Mellitus
Isaac Thorman1, Eric Feldstein1, Aryan Malhotra2, Ariel Sacknovitz1, Staton Albert2, Michael Schubert3, Fawaz Al-Mufti4
1School of Medicine, New York Medical College, 2School of Medicine, Westchester Medical Center, 3Department of Otolaryngology – Head and Neck Surgery, Johns Hopkins University, 4Department of Neurosurgery, Westchester Medical Center at New York Medical College
Objective:
To assess whether glucagon-like peptide 1 (GLP-1) analogues change the risk of developing cognitive impairment among older adults with type 2 diabetes mellitus.
Background:
Increasing prevalences of advanced age, obesity, and diabetes are among the greatest long-term threats to public health in America. GLP-1 analogues have gained popularity in managing both obesity and diabetes, but emerging evidence questions whether these medications may reduce the long-term risks of cerebrovascular disease and cognitive impairment.
Design/Methods:
This retrospective cohort study used the multinational TriNetX Research Network, encompassing ~160 million patients. Type 2 diabetics with no history of cognitive impairment or cerebrovascular disease were included. GLP-1 recipients were compared to non-recipients using Cox proportional hazard models, and patients were followed for up to 10 years. Propensity score matching (1:1) was used to control for potential confounders, with criteria including demographics, BMI, comorbidities, cardiovascular and other diabetic medications, vital signs, and laboratory tests. The competing risk of mortality was assessed using a composite outcome of cognitive impairment and mortality.
Results:
The study included 512,037 patients (88,038 matched). Among matched patients ages 50 years and above, the 10-year risk of cognitive impairment was greater in GLP-1 analogue recipients compared to non-recipients (2.6% vs. 1.3%: HR=2.74; p<0.0001), while the risk of mortality was lower (3.9% vs. 8.2%; HR=0.68; p<0.0001); no difference was observed in the compound outcome (6.1% vs. 9.1%; HR=0.98; p=0.3940). Patients in their 50s saw the greatest benefit, but patients ages 80 and greater showed increases in the risks of both cognitive impairment (10.6% vs. 3.8%; HR=3.39; p<0.0001) and the compound outcome (20.6% vs. 14.5%; HR=1.69; p<0.0001).
Conclusions:
Among older adults with type 2 diabetes, GLP-1 analogues were associated with an increased risk of cognitive impairment secondary to a larger, decreased risk of mortality. However, caution may be warranted in prescribing GLP-1 analogues to the oldest patients.
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