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Recent advances in incretin-based therapy for the treatment of cognitive impairment associated to the type 2 diabetes mellitus: preclinical and clinical studies - a narrative review
Giofrè F, Zaffina I, Pelle MC, Arturi F.. Frontiers in endocrinology, 2025-12-17
Topic: Risk, prevention and care in population studies
It is well-established that individuals with type 2 diabetes mellitus (T2DM) have an increased risk of developing cognitive impairment and dementia, suggesting a close relation between hyperglycemia, insulin resistance, and chronic inflammation. This decline is characterized by a large variety of symptoms going from mild to major form of cognitive impairment characterized of loss of memory, attention, processing speed, and executive function. Preserving the physiological level of glycemia improves cognitive performance, but untreated or inadequately diabetes therapy facilitates the risk of dementia. Some experimental studies have disclosed that drug for diabetes can have protective outcomes on cognitive impairment. In this context, incretin hormone glucagon-like peptide-1 (GLP-1) can reduce blood glucose, improve glucose transport through cell membranes, and to improve brain insulin resistance modulating neuroinflammation. In fact, GLP-1 acts as a neurotransmitter and neuromodulator activating central GLP-1 receptors located in the neurons determining its neurotropic and neuroprotective role in central nervous system. Preclinical and clinical studies suggest the potential role of dipeptidyl peptidase-4 inhibitors (DPP4-i) as therapy for the treatment and prevention of cognitive impairment and dementia. Similarly, several evidences demonstrated that treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduces the risk of cognitive impairment and dementia in T2DM patients by improving learning, memory, attention and executive functions. In addition, preclinical studies suggest a possible neuroprotective effect of GLP-1/GIP dual receptor agonist in animal models. The current narrative review, including studies published from September 1987 to September 2025, summarized the recent improvements regarding to the incretin-based therapy for cognitive impairment associated to the type 2 diabetes mellitus.
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APA 7th
Giofrè, F., Zaffina, I., Pelle, M. C., & Arturi, F. (2025). Recent advances in incretin-based therapy for the treatment of cognitive impairment associated to the type 2 diabetes mellitus: preclinical and clinical studies - a narrative review. Frontiers in endocrinology. https://doi.org/10.3389/fendo.2025.1696419
Vancouver
Giofrè F, Zaffina I, Pelle MC, Arturi F. Recent advances in incretin-based therapy for the treatment of cognitive impairment associated to the type 2 diabetes mellitus: preclinical and clinical studies - a narrative review. Frontiers in endocrinology. 2025. doi:10.3389/fendo.2025.1696419. PMID: 41480353.
BibTeX
@article{giofre2025-41480353,
author = {Giofrè, F. and Zaffina, I. and Pelle, M. C. and Arturi, F.},
title = {{Recent advances in incretin-based therapy for the treatment of cognitive impairment associated to the type 2 diabetes mellitus: preclinical and clinical studies - a narrative review}},
journal = {Frontiers in endocrinology},
year = {2025},
doi = {10.3389/fendo.2025.1696419},
pmid = {41480353},
url = {https://doi.org/10.3389/fendo.2025.1696419}
}
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Key findings
- It is well-established that individuals with type 2 diabetes mellitus (T2DM) have an increased risk of developing cognitive impairment and dementia, suggesting a close relation between hyperglycemia, insulin resistance, and chronic inflammation.
- Similarly, several evidences demonstrated that treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduces the risk of cognitive impairment and dementia in T2DM patients by improving learning, memory, attention and executive functions.
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Study details
- Study designnarrative review
- Evidence strengthLow
How this study scored 45/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 26 of the 58 points we could judge it on, which is 45 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in endocrinology) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | Design recorded as “narrative review”, which our rubric does not rank (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41480353) |
| Free to read | 2 / 2 | Free to read |
| Points | 26 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 26 of the 58 points we could judge it on is 45 out of 100. |
| Total | 45 / 100 | — |
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4 studies in the library carry the topic tag “incretin-based”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 4 tagged studies.