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Anti-diabetic agents and the risks of dementia in patients with type 2 diabetes: a systematic review and network meta-analysis of observational studies and randomized controlled trials
Li Z, Lin C, Cai X, Lv F, Yang W, Ji L. Alzheimer's Research & Therapy, 2024-12-23
Topic: Risk, prevention and care in population studies
Objective To evaluate the association between anti-diabetic agents and the risks of dementia in patients with type 2 diabetes (T2D). Methods Literature retrieval was conducted in PubMed, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrial.gov between January 1995 and October 2024. Observational studies and randomized controlled trials (RCTs) in patients with T2D, which intercompared anti-diabetic agents or compared them with placebo, and reported the incidence of dementia were included. Conventional and network meta-analyses of these studies were implemented. Results were exhibited as the odds ratio (OR) or risk ratio (RR) with 95% confidence interval (CI). Results A total of 41 observational studies (3,307,483 participants) and 23 RCTs (155,443 participants) were included. In the network meta-analysis of observational studies, compared with non-users, sodium glucose cotransporter-2 inhibitor (SGLT-2i) (OR = 0.56, 95%CI, 0.45 to 0.69), glucagon-like peptide-1 receptor agonist (GLP-1RA) (OR = 0.58, 95%CI, 0.46 to 0.73), thiazolidinedione (TZD) (OR = 0.68, 95%CI, 0.57 to 0.81) and metformin (OR = 0.89, 95%CI, 0.80 to 0.99) treatments were all associated with reduced risk of dementia in patients with T2D. The surface under the cumulative ranking curve (SUCRA) evaluation conferred a rank order as SGLT-2i > GLP-1RA > TZD > dipeptidyl peptidase-4 inhibitor (DPP-4i) > metformin > α-glucosidase inhibitor (AGI) > glucokinase activator (GKA) > sulfonylureas > glinides > insulin in terms of the cognitive benefits. Meanwhile, compared with non-users, SGLT-2i (OR = 0.43, 95%CI, 0.30 to 0.62), GLP-1RA (OR = 0.54, 95%CI, 0.30 to 0.96) and DPP-4i (OR = 0.73, 95%CI, 0.57 to 0.93) were associated with a reduced risk of Alzheimer's disease while a lower risk of vascular dementia was observed in patients receiving SGLT-2i (OR = 0.42, 95%CI, 0.22 to 0.80) and TZD (OR = 0.52, 95%CI, 0.36 to 0.75) treatment. In the network meta-analysis of RCTs, the risks of dementia were comparable among anti-diabetic agents and placebo. Conclusion Compared with non-users, SGLT-2i, GLP-1RA, TZD and metformin were associated with the reduced risk of dementia in patients with T2D. SGLT-2i, and GLP-1RA may serve as the optimal choice to improve the cognitive prognosis in patients with T2D.
Key findings
- Results were exhibited as the odds ratio (OR) or risk ratio (RR) with 95% confidence interval (CI).
- Results A total of 41 observational studies (3,307,483 participants) and 23 RCTs (155,443 participants) were included.
- In the network meta-analysis of observational studies, compared with non-users, sodium glucose cotransporter-2 inhibitor (SGLT-2i) (OR = 0.56, 95%CI, 0.45 to 0.69), glucagon-like peptide-1 receptor agonist (GLP-1RA) (OR = 0.58, 95%CI, 0.46 to 0.73), thiazolidinedione (TZD) (OR = 0.68, 95%CI, 0.57 to 0.81) and metformin (OR = 0.89, 95%CI, 0.80 to 0.99) treatments were all associated with reduced risk of dementia in patients with T2D.
- Meanwhile, compared with non-users, SGLT-2i (OR = 0.43, 95%CI, 0.30 to 0.62), GLP-1RA (OR = 0.54, 95%CI, 0.30 to 0.96) and DPP-4i (OR = 0.73, 95%CI, 0.57 to 0.93) were associated with a reduced risk of Alzheimer's disease while a lower risk of vascular dementia was observed in patients receiving SGLT-2i (OR = 0.42, 95%CI, 0.22 to 0.80) and TZD (OR = 0.52, 95%CI, 0.36 to 0.75) treatment.
- Conclusion Compared with non-users, SGLT-2i, GLP-1RA, TZD and metformin were associated with the reduced risk of dementia in patients with T2D.
Why it matters
This network meta-analysis of 41 observational studies and 23 randomized controlled trials found that SGLT-2 inhibitors, GLP-1 receptor agonists, thiazolidinediones, and metformin were all associated with reduced dementia risk in people with type 2 diabetes. It suggests several diabetes drugs may be linked to lower dementia risk, but it does not establish that any of them treat or cure dementia.
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Study details
- Study designmeta-analysis
- Participants3,462,926
- Effect sizeObservational: SGLT2i OR 0.56 (95% CI 0.45-0.69), GLP-1RA OR 0.58 (0.46-0.73) vs non-users; RCTs: no difference
- Evidence strengthModerate
Limitations
Observational estimates prone to confounding by indication and time-related bias; RCTs were not designed for dementia outcomes and had short follow-up.
How this study scored 65/100
Published in a peer-reviewed journal, and it is a meta-analysis pooling many studies. We have no data on free to read, so that was left out: it earned 64 of the 98 points we could judge it on, which is 65 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer's Research & Therapy) |
| Journal's citation record | 1 / 4 | Alzheimer s Research & Therapy: journal h-index 146 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 4 / 4 | 3,462,926 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | A review of other studies — randomisation is not credited here |
| Times cited | 3 / 7 | Cited 36 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 9.0 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 3 / 6 | Cited 3.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 2 / 4 | Cited 36 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Linong Ji: h-index 56 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Peking University People's Hospital: institution h-index 335 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39716328) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 64 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 64 of the 98 points we could judge it on is 65 out of 100. |
| Total | 65 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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APA 7th
Li, Z., Lin, C., Cai, X., Lv, F., Yang, W., & Ji, L. (2024). Anti-diabetic agents and the risks of dementia in patients with type 2 diabetes: a systematic review and network meta-analysis of observational studies and randomized controlled trials. Alzheimer's Research & Therapy. https://doi.org/10.1186/s13195-024-01645-y
Vancouver
Li Z, Lin C, Cai X, Lv F, Yang W, Ji L. Anti-diabetic agents and the risks of dementia in patients with type 2 diabetes: a systematic review and network meta-analysis of observational studies and randomized controlled trials. Alzheimer's Research & Therapy. 2024. doi:10.1186/s13195-024-01645-y. PMID: 39716328.
BibTeX
@article{li2024-39716328,
author = {Li, Z. and Lin, C. and Cai, X. and Lv, F. and Yang, W. and Ji, L.},
title = {{Anti-diabetic agents and the risks of dementia in patients with type 2 diabetes: a systematic review and network meta-analysis of observational studies and randomized controlled trials}},
journal = {Alzheimer's Research \& Therapy},
year = {2024},
doi = {10.1186/s13195-024-01645-y},
pmid = {39716328},
url = {https://doi.org/10.1186/s13195-024-01645-y}
}
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