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Medications for adults with type 2 diabetes: a living systematic review and network meta-analysis
Kailei Nong, Britta Tendal Jeppesen, Qingyang Shi, Thomas Agoritsas, Gordon H Guyatt, Heath White, Yiyuan Gao, Arnav Agarwal et al.. BMJ (Clinical research ed.), 2025-08-14
Topic: Drug trials: efficacy and safety
The systematic review and NMA includes 493 168 participants from 869 trials (adding 53 trials since October 2022) reporting data for 13 drug classes (63 drugs) and 26 outcomes of interest. Regarding benefits, moderate to high certainty evidence confirms the well established cardiovascular and kidney benefits of sodium-glucose cotransporter-2 (SGLT-2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and finerenone (the last for patients with established chronic kidney disease). The most effective drugs in reducing body weight were tirzepatide (mean difference (MD) -8.63 kg (95% confidence interval -9.34 to -7.93); moderate certainty) and orforglipron (MD -7.87 kg (-10.24 to -5.50); low certainty), followed by eight other GLP-1RAs (high to moderate certainty). Absolute benefits of medications vary substantially depending on the baseline risk of cardiovascular and kidney outcomes; risk-stratified absolute effects of medications are summarised using an interactive multiple comparisons tool (https://matchit.magicevidence.org/250709dist-diabetes/#!/). Regarding medication-specific harms, SGLT-2 inhibitors increase genital infections (odds ratio (OR) 3.29 (95% CI 2.88 to 3.77); high certainty) and ketoacidosis due to diabetes (OR 2.08 (1.45 to 2.99); high certainty), and probably increase amputations (OR 1.27 (1.01 to 1.61); moderate certainty); tirzepatide and GLP-1RAs probably increase severe gastrointestinal events (most increased risk with tirzepatide (OR 4.21 (1.87 to 9.49); moderate certainty)); finerenone increases severe hyperkalaemia (OR 5.92 (3.02 to 11.62); high certainty); and thiazolidinediones increase major osteoporotic fractures and probably increase hospitalisation for heart failure. Sulfonylureas, insulin, and dipeptidyl peptidase-4 inhibitors probably increase the risk of severe hypoglycaemia. There is low to very low certainty evidence for effects on other diabetes-related complications, including neuropathy and visual impairment. Despite interest in the issue, there is uncertainty about whether GLP-1RAs may reduce dementia (OR 0.92 (0.83 to 1.02); low certainty). This living systematic review provides a comprehensive summary of the cardiovascular, kidney, and weight loss benefits, as well as medication-specific harms of medications for adults with type 2 diabetes, including effects of SGLT-2 inhibitors, GLP-1RAs, finerenone and tirzepatide. SYSTEMATIC REVIEW REGISTRATION: PROSPERO number: CRD42022325948. A more detailed proto
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Nong, K., Jeppesen, B. T., Shi, Q., Agoritsas, T., Guyatt, G. H., White, H., et al. (2025). Medications for adults with type 2 diabetes: a living systematic review and network meta-analysis. BMJ (Clinical research ed.). https://doi.org/10.1136/bmj-2024-083039
Vancouver
Nong K, Jeppesen BT, Shi Q, Agoritsas T, Guyatt GH, White H, et al. Medications for adults with type 2 diabetes: a living systematic review and network meta-analysis. BMJ (Clinical research ed.). 2025. doi:10.1136/bmj-2024-083039. PMID: 40813122.
BibTeX
@article{nong2025-40813122,
author = {Nong, Kailei and Jeppesen, Britta Tendal and Shi, Qingyang and Agoritsas, Thomas and Guyatt, Gordon H and White, Heath and Gao, Yiyuan and Agarwal, Arnav and others},
title = {{Medications for adults with type 2 diabetes: a living systematic review and network meta-analysis}},
journal = {BMJ (Clinical research ed.)},
year = {2025},
doi = {10.1136/bmj-2024-083039},
pmid = {40813122},
url = {https://doi.org/10.1136/bmj-2024-083039}
}
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Key findings
- The systematic review and NMA includes 493 168 participants from 869 trials (adding 53 trials since October 2022) reporting data for 13 drug classes (63 drugs) and 26 outcomes of interest.
- Regarding benefits, moderate to high certainty evidence confirms the well established cardiovascular and kidney benefits of sodium-glucose cotransporter-2 (SGLT-2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and finerenone (the last for patients with established chronic kidney disease).
- The most effective drugs in reducing body weight were tirzepatide (mean difference (MD) -8.63 kg (95% confidence interval -9.34 to -7.93); moderate certainty) and orforglipron (MD -7.87 kg (-10.24 to -5.50); low certainty), followed by eight other GLP-1RAs (high to moderate certainty).
- Absolute benefits of medications vary substantially depending on the baseline risk of cardiovascular and kidney outcomes; risk-stratified absolute effects of medications are summarised using an interactive multiple comparisons tool (https://matchit.magicevidence.org/250709dist-diabetes/#!/).
- Regarding medication-specific harms, SGLT-2 inhibitors increase genital infections (odds ratio (OR) 3.29 (95% CI 2.88 to 3.77); high certainty) and ketoacidosis due to diabetes (OR 2.08 (1.45 to 2.99); high certainty), and probably increase amputations (OR 1.27 (1.01 to 1.61); moderate certainty); tirzepatide and GLP-1RAs probably increase severe gastrointestinal events (most increased risk with tirzepatide (OR 4.21 (1.87 to 9.49); moderate certainty)); finerenone increases severe hyperkalaemia (OR 5.92 (3.02 to 11.62); high certainty); and thiazolidinediones increase major osteoporotic fractures and probably increase hospitalisation for heart failure.
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Study details
- Study designsystematic review
- Participants168
- Effect sizeOR 2.08; OR 1.27; OR 4.21
- Evidence strengthHigh
How this study scored 89/100
Published in a leading specialty journal, and it is a systematic review of all the studies on the question. 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, multi-centre collaboration and free to read, so those were left out: it earned 50 of the 56 points we could judge it on, which is 89 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (BMJ (Clinical research ed.)) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 12 / 12 | A systematic review of all the studies on the question |
| Strength of evidence | 5 / 5 | Rated “high” 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 | 2 / 4 | 168 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 | — / 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 |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40813122) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 50 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 50 of the 56 points we could judge it on is 89 out of 100. |
| Total | 89 / 100 | — |
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