Glucagon-Like Peptide-1 Receptor Agonists and Incidence of Dementia Among Older Adults With Type 2 Diabetes : A Target Trial Emulation
Authors' conclusion
Among older adults with diabetes, no clear evidence was found that the incidence of dementia differed overall between patients using GLP-1RAs versus DPP4is. Under conventional statistical criteria, an effect of GLP-1RAs between a 39% decrease and a 5% increase in risk for dementia was highly compatible with the data, although estimates differed by age. Randomized trials are needed to quantify the effect of GLP-1RAs on dementia.
Study context
- Population
- Medicare fee-for-service beneficiaries aged ≥66 years with diabetes using metformin, without dementia at baseline, initiating GLP-1RAs or DPP4is Jan 2017–Dec 2018, US; mean age 71 years, 55% femalematched 1:2
- Participants
- 2,418 vs 4,836
- Comparison
- GLP-1 RA vs DPP-4i as second-line therapy for T2D
- GLP-1RAn = 2,418
- DPP4in = 4,836reference
- Outcome
- Risk of dementia (onset defined as 1 year before date of new dementia diagnosis)
- Follow-up
- 30 months
Methodological detailspropensity-score matched 1:2
- Propensity-score matched 1:2
Main finding
As reported in the abstract
Dementia
GLP-1RA
96
events
DPP4i
217
events
Risk difference, percentage points (95% CI)
Between GLP-1RA and DPP4i
−0.93(−2.33 to 0.23)
Risk ratio (95% CI)
GLP-1RAvs DPP4i
0.83(0.61–1.05)
Further findings
Dementia risk, subgroup aged <75 years · 30 months
- Estimated risk ratio, age <75 years
- 0.64 (95% CI, 0.46 to 0.93)
Dementia risk, subgroup aged ≥75 years · 30 months
- Estimated risk ratio, age ≥75 years
- 1.22 (95% CI, 0.74 to 1.66)
Original publication
Glucagon-Like Peptide-1 Receptor Agonists and Incidence of Dementia Among Older Adults With Type 2 Diabetes : A Target Trial Emulation. Ann Intern Med. Published 22 July 2025. doi:10.
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