Study links tirzepatide to lower dementia risk than semaglutide in type 2 diabetes
A large records-based study found lower two-year dementia rates with tirzepatide than with semaglutide or SGLT2 inhibitors, but the authors say it cannot prove cause and effect.
Tirzepatide (sold as Mounjaro for type 2 diabetes and Zepbound for weight loss) was associated with a lower two-year risk of dementia than semaglutide (Ozempic, Wegovy and Rybelsus) in adults with type 2 diabetes, according to a study published in Diabetes Research and Clinical Practice [1][2]. The same analysis found tirzepatide was associated with a lower dementia risk than a class of diabetes drugs called SGLT2 inhibitors [1].
The paper is open access and its authors are listed as Alhena Younis, Alex E. Henney, David R. Riley and colleagues, including Uazman Alam [1][2]. It appears in the journal's May 2026 issue as article 113083 [2].
The team ran three "target trial emulations," a method that uses existing patient records to imitate how a randomized trial would be set up, using real-world data from the TriNetX global federated network [1]. Everyone included was an adult with type 2 diabetes who did not have a dementia diagnosis at the start, and each was followed for two years [1]. The researchers tracked a first diagnosis of dementia, major adverse cardiovascular events (MACE) and death from any cause, comparing groups after propensity score matching, a statistical step meant to make the groups more alike [1].
After matching, the comparison of tirzepatide with SGLT2 inhibitors included 14,462 patients; the comparison of semaglutide with SGLT2 inhibitors included 57,959; and the comparison of tirzepatide with semaglutide included 12,246 [1].
Tirzepatide was associated with a lower dementia risk than semaglutide, with a hazard ratio of 0.69 (95% confidence interval 0.48 to 0.99, p = 0.04), and lower than SGLT2 inhibitors, with a hazard ratio of 0.66 (95% CI 0.47 to 0.93, p = 0.02) [1]. A hazard ratio below 1.0 means fewer events in the tirzepatide group over the same period. The upper end of the confidence interval for the semaglutide comparison, 0.99, sits just under 1.0, which means the result is close to the line where no difference would be seen.
Death from any cause was also lower with tirzepatide: a hazard ratio of 0.72 (95% CI 0.58 to 0.90, p < 0.01) compared with semaglutide, and 0.29 (95% CI 0.23 to 0.37, p < 0.01) compared with SGLT2 inhibitors [1]. The authors report that both tirzepatide and semaglutide reduced MACE compared with SGLT2 inhibitors [1].
The abstract does not report a dementia hazard ratio for the semaglutide-versus-SGLT2-inhibitor comparison, so it is not known from this paper how those two groups compared on that specific outcome [1].
The authors describe their findings as hypothesis-generating and say they require confirmation in randomized controlled trials [1]. The study looked back at records rather than assigning treatments by chance, so factors not captured in the data could still explain part of the difference. Absolute dementia rates, the doses patients received and how long they took each drug are not reported in the abstract [1].
Why it matters for patients
Type 2 diabetes is a recognized risk factor for cognitive decline, and Mounjaro, Zepbound, Ozempic, Wegovy and Rybelsus are among the most widely prescribed drugs in the country, so any difference in dementia rates between them gets attention. This study reports an association, not proof that one drug protects the brain better than another. No GLP-1 or SGLT2 inhibitor is approved to prevent or treat dementia, and the research does not show that switching from semaglutide to tirzepatide would change anyone's dementia risk.
One practical limit is who was studied: all participants had type 2 diabetes, so the results do not directly describe people who take these medicines only for weight loss. The abstract also gives no absolute numbers, so how many actual dementia cases were involved, and how large the difference was in percentage terms, has not been reported [1].
What happens next
The authors say randomized controlled trials are needed to test whether the difference holds up [1]. Whether such a head-to-head trial of tirzepatide and semaglutide with dementia as an outcome has been planned or started has not been disclosed in the paper [1][2].
Sources
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