GLP-1 Therapy May Reduce Dementia Risk
Further studies are needed to further confirm the association between glucagon-like peptide 1 medication and reductions in dementia risk.
Diabetes is considered a risk factor for dementia, “estimated to account for approximately 5% of the population-attributable fraction of all dementia,” according to authors of a study published in JAMA Neurology. Therefore, investigators aimed to determine if cardioprotective glucose-lowering agents could reduce the risk of dementia or cognitive impairment.1
Further studies are needed to further confirm the association between glucagon-like peptide 1 medication and reductions in dementia risk. Image Credit: LIGHTFIELD STUDIOS - stock.adobe.com
Although the investigators found that cardioprotective glucose-lowering therapies were not associated with an overall reduction in dementia, glucagon-like peptide-1 (GLP-1) receptor agonists were associated with statistically significant reductions in all-cause dementia in a meta-analysis of randomized clinical trials.1
Research has shown that type 2 diabetes can increase a patient’s risk of developing dementia and can be associated with the length of time and how severe their diabetes is. Furthermore, type 1 diabetes might also increase the risk of developing dementia, according to the Alzheimer’s Society.2
The investigators of the current study used PubMed and Embase databases for articles published from inception to June 11, 2024, and included randomized clinical trials that included adults 18 years and older, evaluating cardioprotective glucose-lowering therapies. The studies also had reported dementia, cognitive impairment, and/or change in cognitive score and a 6-month minimum follow-up duration, according to the study authors. The primary outcome included dementia or cognitive impairment at follow-up, and secondary outcomes included dementia subtypes and change in cognitive score.1
There were 3831 articles published before June 11, 2024, and 505 were considered potentially relevant. In total, 26 trials were included, but 3 were only for the secondary outcome of change in cognitive score alone. In total, 164,531 individuals were included with a mean age of 64.4 years, and 34.9% were women. The median follow-up was 31.4 months, and the publication years ranged from 2015 to 2024. Overall, the investigators categorized the risk of bias as low for all trials.1
Twenty-three articles were included for the primary end point, including 160,191 individuals, with 12 trials evaluating sodium-glucose cotransporter 2 (SGLT2) inhibitors, 10 evaluating GLP-1s, and 1 evaluating pioglitazone. There were 93 individuals in the intervention group that had dementia or cognitive impairment and 119 in the control group. Investigators found that the glucose-lowering therapy was not significantly associated with reductions in dementia or cognitive impairment; however, glucose-lowering therapy with GLP-1s was statistically significant (OR, 0.55 [95% CI, 0.35-0.86]).1
For dementia subtype, 10 trials were included for vascular dementia (94,648 patients), with only 6 individuals in the intervention group and 15 in the control group being diagnosed with vascular dementia. For Alzheimer dementia (115,840 patients in 12 studies), 56 patients in the intervention group and 51 in the control group were diagnosed, and for Lewy body dementia (47,287 patients in 4 studies), 1 individual in the intervention group and 3 in the control group were diagnosed. The investigators reported that glucose-lowering agents were not significantly associated with reductions for any of these dementia subtypes. As for the 3 trials for change in cognitive score, there were no significant differences in cognition.1
“A larger risk reduction in dementia was associated with randomization to receive GLP-1RAs than SGLT2i classes,” the investigators concluded.1 “This may be partly explained by differences in populations enrolled, with a higher all-cause dementia event rate noted among the control group of GLP-1RA trials compared with SGLT2i trials (0.14% vs 0.05%), with a resultant increase in statistical power to detect associations.”
The investigators state that future studies should report dementia outcomes by APOE4 status and sex in order to determine the efficacy of glucose-lowering therapies for dementia as metabolism may differ for these groups.1
READ MORE: Neurology Resource Center
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