GLP-1RAs and SGLT2is Associated with Lower Dementia Risk in People with Type 2 Diabetes
Treatment with glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) was associated with a significantly reduced risk of developing Alzheimer disease and related dementias (ADRD) in individuals people diagnosed with type 2 diabetes mellitus (T2D) according to results of a retrospective population-based cohort study published in JAMA Neurology. The findings suggest a neuroprotective effect of treatment with GLP-1Ras and SGLT2is, with potential applications in ADRD prevention for people with T2D.
The retrospective study used data from the OneFlorida+ Clinical Research Consortium data repository from 2014 to 2023. Eligible adult participants aged ≥50 years with T2D undergoing treatment with GLP-1RAs, SGLT2is, or other glucose lowering drugs (GLDs) with no prior ADRD diagnosis were included in the study. Researchers divided the study population into 3 cohorts to compare risk of ADRD:
- The first cohort (n=33,858) included participants treated with GLP-1RAs (n=10,212) vs other GLDs (n=23,646).
- The second cohort (n=34,185) included participants treated with SGLT2is (n=10,524) vs other GLDs (n=23,661).
- The third cohort (n=24,117) included participants treated with GLP-1RAs (n=11,395) vs SGLT2is (n=12,722).
In terms of results:
- Participants treated with GLP-1RAs had a 33% lower risk of developing ADRD (rate difference [RD], -2.26 per 1000 person-years [95% CI, -2.88 to -1.64]; hazard ratio [HR], 0.67 [95% CI, 0.47 to 0.96]) compared with those taking other GLDs.
- Those treated with SGLT2is had a 43% lower risk of developing ADRD (RD, -3.05 per 1000 person-years [95% CI, -3.68 to -2.42]; HR, 0.57 [95% CI, 0.43 to 0.75]) compared to those treated with other GLDS.
- There was no statistically significant difference seen between participants treated with GLP-1RAs and those treated with SGLT2is in terms of the risk of developing ADRD.
These results were consistent across multiple sensitivity and subgroup analyses.