Ann Intern Med

No clear evidence that GLP-1RAs are superior to DPP4i drugs at lowering dementia risk in older patients with diabetes

July 24, 2025

No clear statistical signal supported a conclusion that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were linked to a reduction in dementia—compared with dipeptidyl peptidase-4 inhibitors (DPP4is)—in older adults starting second-line therapy for diabetes, according to this target trial emulation study. Authors note that confounding is possible due to absent data on BMI and glycemic control, as well as the short follow-up period. Randomized controlled trials would be required to quantify effects of GLP-1 RAs on dementia risk.

Study details. This U.S. target-trial emulation study involved data on 2,418 fee-for-service Medicare beneficiaries (age, ≥66 years; mean age, 71 years; female, 55%) without dementia on metformin for diabetes who started GLP-1 RAs. These data were compared with data on 4,836 matched controls starting on DPP4is. The trial spanned January 2016 to December 2020; median follow-up was 1.9 years. Dementia onset was defined as a year prior to the date of dementia diagnosis.

Results. Estimated risk difference at 30 months: −0.93 (95% confidence interval [CI], −2.33-0.23) % points. Estimated risk ratio: 0.83 (95% CI, 0.61-1.05). In patients <75 years old, the estimated risk ratio was 0.64 (95% CI, 0.46-0.93) vs. 1.22 (95% CI, 0.74-1.66) in patients ≥75 years.

Source:

Inoue K, et al. (2025, July 22). Ann Intern Med. Glucagon-Like Peptide-1 Receptor Agonists and Incidence of Dementia Among Older Adults With Type 2 Diabetes : A Target Trial Emulation. https://pubmed.ncbi.nlm.nih.gov/40690769/