Isaac Thorman<\/b><\/strong><\/p>\n<\/div>\n Thorman also noted that although the phase 3 Evoke randomized controlled trial found improvements in biomarkers related to Alzheimer\u2019s disease with semaglutide among older adults with mild cognitive impairment or Alzheimer\u2019s disease, the progression of Alzheimer\u2019s disease was not delayed. <\/p>\n
\u201cFor this reason, our objective was to assess the long-term risk of cognitive impairment associated with GLP-1 analog use in older adults with type 2 diabetes,\u201d Thorman said. <\/p>\n
Using the TriNetX Research Network, the researchers matched 64,530 patients aged 50 years and older with type 2 diabetes using GLP-1 analogs with those who were not using these drugs and followed them for up to 10 years. <\/p>\n
\u201cGLP-1 analog use was associated with an increased risk of cognitive impairment,\u201d Thorman said. \u201cHowever, this appeared to be secondary to the more significant decreased risk of mortality.\u201d <\/p>\n
Risks for cognitive impairment increased 2.6% for those on GLP-1 analogs and 1.3% for those not on them (HR = 2.74; P<\/i> < .0001). Risks for mortality increased by 3.9% for those on GLP-1 analogs and 8.2% for those not on them (HR = 0.68; P<\/i> < .0001). <\/p>\n
\u201cOn creation of a compound outcome to assess the competing risk of these two outcomes against one another, we found no significant change,\u201d Thorman said. \u201cWe interpret this to mean that GLP-1 analog recipients lived significantly longer than non-recipients, but they lived long enough to develop cognitive impairment.\u201d <\/p>\n
However, Thorman noted specific caveats emerging from the stratified analysis. <\/p>\n
\u201cBy age, we found no protective effect among patients in their 80s, while patients in their 50s had no change in the risk of cognitive impairment,\u201d he said. <\/p>\n
Also, patients with BMI of 50 and higher did not have any changes in their risks. <\/p>\n
\u201cBy sex, we found the increased risk of cognitive impairment was greater among female patients than among male patients,\u201d Thorman continued. <\/p>\n
Increased risks for cognitive impairment for women were balanced by the mortality benefit of treatment, he said, but the mortality benefit outweighed risks for cognitive impairment among men. <\/p>\n
\u201cAnd by A1c, we found that the mortality protection was only observed in patients with an A1c of at least 6.5%,\u201d Thorman said. <\/p>\n
Based on this data, Thorman concluded that the association between GLP-1 analog use and cognitive impairment was secondary to the drugs\u2019 protective effect against mortality, with specific patient factors driving outcomes. <\/p>\n
\u201cWe interpret this as an overall favorable profile for GLP-1 analogs,\u201d he said. <\/p>\n
Also, this survival paradox, the study\u2019s sample size and its long-term follow-up may explain the lack of significance found in randomized controlled trials, Thorman said, but he did recommend caution in interpreting these results. <\/p>\n
\u201cCausality cannot be inferred in this retrospective analysis,\u201d he said. \u201cProspective randomized trials remain essential.\u201d <\/p>\n
For more information:<\/b> <\/p>\n
Isaac Thorman, MSc<\/b>, <\/b>can be reached at ithorman@student.nymc.edu.<\/p>\n\n
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Sources\/Disclosures<\/h3>\n Source: <\/h2>\n Thorman IB, et al. Long-term risk of cognitive impairment with GLP-1 analogues in older adults with type 2 diabetes mellitus. Presented at: American Academy of Neurology Annual Meeting; April 5-9, 2025; San Diego. <\/p>\n
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