Medications for adults with type 2 diabetes: a living systematic review and network meta-analysis
Authors' conclusion
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.
Study context
- Population
- Adults with T2D; RCTs of ≥24 weeks; Medline and Embase searched up to 31 July 2024
- Participants
- 493,168 adults869 trials
- Comparison
- Medications for T2D vs standard treatment, placebo or each other
- Outcome
- Body weight
Methodological detailsfrequentist random effects, GRADE, updates planned at least two times a year
- Frequentist random effects
- GRADE
- Updates planned at least two times a year
Pooled result
As reported in the abstract
Each group vs standard treatment or placeboMD, kg (95% CI)
Tirzepatidemoderate certainty
−8.63(−9.34 to −7.93)
Orforglipronlow certainty
−7.87(−10.24 to −5.50)
Further pooled results
| Outcome | OR (CI) | |
|---|---|---|
| DementiaGLP-1RAsvs Standard treatment or placebo | 0.92 (0.83–1.02) | |
| 0.512Odds ratio (log scale) |
- Dementia: low certainty; uncertain whether GLP-1RAs may reduce dementia
CV and kidney outcomes
- Moderate to high certainty evidence confirms CV and kidney benefits of SGLT-2 inhibitors, GLP-1RAs and finerenone (the last for established CKD)
- Absolute benefits vary substantially with baseline CV and kidney risk
Other diabetes-related complications incl. neuropathy and visual impairment
- Low to very low certainty evidence for effects
Safety
| Outcome | OR (95% CI) | |
|---|---|---|
| Medication-specific harmsSGLT-2 inhibitorsvs Standard treatment or placeboGenital infections; high certainty | 3.29 (2.88–3.77) | |
| Medication-specific harmsSGLT-2 inhibitorsvs Standard treatment or placeboDKA; high certainty | 2.08 (1.45–2.99) | |
| Medication-specific harmsSGLT-2 inhibitorsvs Standard treatment or placeboAmputations; moderate certainty (probably increase) | 1.27 (1.01–1.61) | |
| Medication-specific harmsTirzepatidevs Standard treatment or placeboSevere GI events; moderate certainty (most increased risk) | 4.21 (1.87–9.49) | |
| Medication-specific harmsFinerenonevs Standard treatment or placeboSevere hyperkalaemia; high certainty | 5.92 (3.02–11.62) | |
| 0.050.21520Odds ratio (log scale) |
Medication-specific harms
- Tirzepatide and GLP-1RAs probably increase severe GI events
- Thiazolidinediones increase major osteoporotic fractures and probably increase HF hospitalisation
- Sulfonylureas, insulin and DPP-4 inhibitors probably increase severe hypoglycaemia
Original publication
Medications for adults with type 2 diabetes: a living systematic review and network meta-analysis. BMJ. Published 14 August 2025. doi:10.
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