Target trial emulations for tirzepatide, semaglutide and SGLT2-inhibitors for dementia in patients with type 2 diabetes: Real world evidence from a retrospective cohort study

Jan 16, 2026Diabetes research and clinical practice

Comparing tirzepatide, semaglutide, and SGLT2 inhibitors for dementia risk in people with type 2 diabetes using real-world patient data

AI simplified

GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗

Abstract

Tirzepatide was associated with a lower risk of dementia versus semaglutide and SGLT2 inhibitors in type 2 diabetes patients.

In a cohort of 14,462 patients, tirzepatide showed a hazard ratio of 0.69 for dementia risk compared to semaglutide.
Tirzepatide demonstrated a hazard ratio of 0.66 for dementia risk compared to SGLT2 inhibitors.
Tirzepatide was associated with lower all-cause mortality, with a hazard ratio of 0.72 compared to semaglutide and 0.29 compared to SGLT2 inhibitors.
Both tirzepatide and semaglutide were linked to reduced major adverse cardiovascular events compared to SGLT2 inhibitors.

AI simplified

AIMS: Evidence suggests sodium glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists reduce the dementia onset/progression. The dual GLP1/GIP receptor agonist, tirzepatide's effect on dementia outcomes remains unknown. We compared tirzepatide, semaglutide and SGLT2-i head-to-head in relation to incident dementia in type 2 diabetes patients METHODS: Three target trial emulations (TTE) were conducted using real-world data from the TriNetX global federated network: TTE1: tirzepatide vs. SGLT2-i, TTE2: semaglutide vs. SGLT2-i and TTE3: tirzepatide vs. semaglutide. Eligible adults with type 2 diabetes and no baseline dementia were included. Follow-up was two years. First diagnosis of dementia, MACE, and all-cause mortality were analysed using survival analysis after propensity score matching.

RESULTS: After matching, TTE1 included 14,462 patients; TTE2, 57,959; TTE3 12,246. Tirzepatide was associated with lower risk of dementia versus semaglutide (HR 0.69, 95% CI 0.48-0.99, p = 0.04) and SGLT2-i (HR 0.66, 95% CI 0.47-0.93, p = 0.02), and lower mortality (HR 0.72, 95% CI 0.58-0.90, p < 0.01; HR 0.29, 95% CI 0.23-0.37, p < 0.01). Tirzepatide and semaglutide reduced MACE vs SGLT2-i.

CONCLUSIONS: Tirzepatide is associated with a lower risk of dementia versus semaglutide and SGLT2-I in type 2 diabetes. Findings are hypothesis generating, requiring confirmation in randomised controlled trials.

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

Target trial emulations for tirzepatide, semaglutide and SGLT2-inhibitors for dementia in patients with type 2 diabetes: Real world evidence from a retrospective cohort study

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief