TOPLINE:
When used as first-line therapy in patients with type 2 diabetes (T2D), GLP-1 receptor agonists (RAs) seemed to be more effective than metformin at reducing the risk for dementia, particularly Alzheimer’s disease and other nonvascular types, with this benefit being more pronounced in older adults and women.
METHODOLOGY:
- Both GLP-1 RAs and metformin have shown potential neuroprotective effects in patients with T2D, but no direct comparisons have evaluated their relative efficacy in preventing dementia.
- Researchers conducted a retrospective cohort study using data from a global health research network to compare the risk for dementia in patients with T2D who initiated either GLP-1 RAs or metformin as first-line monotherapy between 2004 and 2024.
- They included 87,229 propensity score-matched patients receiving either therapy for at least 6 consecutive months; age (mean, approximately 58 years), sex distribution (approximately 36% men), comorbidity profiles, and metabolic parameters were comparable between treatment groups.
- The index date was defined as the first prescription date of GLP-1 RAs or metformin following a diagnosis of T2D; at least 24 months of follow-up after a 6-month washout period from the index date was required.
- The primary outcome measure was the incidence of overall dementia, whereas secondary outcomes included the incidence of specific dementia subtypes such as vascular dementia, Alzheimer’s disease, and other forms.
TAKEAWAY:
- The use of GLP-1 RAs was associated with a lower risk for incident overall dementia (adjusted hazard ratio [HR], 0.90; 95% CI, 0.85-0.95) than the use of metformin.
- Compared with metformin, GLP-1 RAs were linked to a reduced risk for incident Alzheimer’s disease and nonvascular dementia, but the risk for vascular dementia did not differ between the treatment groups.
- The protective effects of GLP-1 RAs for dementia were more prominent in adults aged 60 years or older and in women.
- Rates of all-cause mortality were also notably lower in the GLP-1 RA group than in the metformin group (adjusted HR, 0.89; 95% CI, 0.81-0.95).
IN PRACTICE:
“Given the severe societal, familial, and economic burden of diabetes-related dementia, these findings raise important considerations about the role of GLP-1 RAs as first-line therapies in T2DM management,” the authors wrote.
SOURCE:
This study was led by Mingyang Sun, People’s Hospital of Zhengzhou University in Zhengzhou, China. It was published online in BMJ Open Diabetes Research & Care.
LIMITATIONS:
The reliance on deidentified electronic health records may have introduced variability in diagnostic coding. The exclusion of patients with prior exposure to GLP-1 RAs or metformin may have limited generalizability to those with mixed treatment histories. The follow-up period, while sufficient for observing dementia outcomes, may not have fully captured long-term cognitive effects.
DISCLOSURES:
The research received support from the National Natural Science Foundation of China, the National Key Research and Development Program of China, and the Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital. The authors declared no conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.