Effectiveness and safety of combining SGLT2 inhibitors and GLP-1 receptor agonists in individuals with type 2 diabetes: a systematic review and meta-analysis of cohort studies
Pooled result · MACEResult — go to the resultRelative risk 0.56 95% CI 0.43–0.71Authors' conclusion
Observational studies suggest that combining an SGLT2 inhibitor and a GLP-1 RA in type 2 diabetes may lower the risk of MACE, all-cause and cardiovascular mortality, hospitalisation for heart failure and kidney composite endpoints compared with monotherapy with either drug. Of course, residual confounding cannot be overcome but results support the need for future randomised trials of combined vs monotherapy.
Study context
- Population
- Individuals with T2D in cohort studies with maximum follow-up ≥1 year; studies enrolling T1D excluded; PubMed and Embase searched to 1 May 2025
- Participants
- 1,164,774 individuals18 cohort studies
- Comparison
- SGLT2i + GLP-1 RA combination therapy vs SGLT2i or GLP-1 RA monotherapy
- Outcome
- Composite of major adverse cardiovascular events (MACE)
Methodological detailsrandom effects meta-analysis, ROBINS-I risk of bias, Grading of Recommendations Assessment, Development and Evaluation (GRADE) certainty of evidence
- Random effects meta-analysis
- ROBINS-I risk of bias
- GRADE certainty of evidence
Pooled result
MACE
Relative risk
0.56
95% CI 0.43–0.71
Combination therapyvs Monotherapy
RR 0.56 (95% CI 0.43–0.71)
As reported in the abstract
Further pooled results
| Outcome | RR (95% CI) | |
|---|---|---|
| Kidney composite endpointVery low certainty of evidence | 0.48 (0.32–0.73) | |
| All-cause mortalityLow certainty of evidence | 0.50 (0.40–0.63) | |
| CV mortalityLow certainty of evidence | 0.26 (0.16–0.43) | |
| Hospitalisation for HFModerate certainty of evidence | 0.67 (0.64–0.71) | |
| 0.10.31310Relative risk (log scale) |
Safety
- Safety data could not be pooled due to lack of events; no differences observed in risk of severe hypoglycaemia, DKA, genitourinary infections and gastrointestinal side effects
- No data reported on serious adverse events or major adverse limb events
Original publication
Effectiveness and safety of combining SGLT2 inhibitors and GLP-1 receptor agonists in individuals with type 2 diabetes: a systematic review and meta-analysis of cohort studies. Diabetologia. Published 21 October 2025. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →