Cardiovascular and renal outcomes of dual combination therapies with glucagon-like peptide-1 receptor agonists and sodium-glucose transport protein 2 inhibitors: a systematic review and meta-analysis
Authors' conclusion
Combination therapy with GLP-1RA, SGLT2i, or finerenone confers cardiorenal protection beyond monotherapy in T2D, as supported by concordant evidence from RCTs and large real-world cohorts. These findings support broader clinical adoption of dual-agent strategies but also underscore the need for dedicated prospective trials powered to assess hard clinical outcomes with dual-agent strategies.
Study context
- Population
- Studies of combination regimens with GLP-1 RA, SGLT2i and/or finerenone vs monotherapies (T2D)4 post hoc RCT analyses · 10 observational studies
- Comparison
- Dual combination therapy vs corresponding monotherapies
- Outcome
- Cardiorenal outcomes, observational studies
Methodological detailsrandom-effects meta-regression (RCTs), random-effects meta-analyses (observational studies), MEDLINE and Embase searched
- Random-effects meta-regression (RCTs)
- Random-effects meta-analyses (observational studies)
- MEDLINE and Embase searched
Pooled result
As reported in the abstract
Hazard ratio (95% CI)
GLP-1RA + SGLT2ivs SGLT2i monotherapyMACE
0.59(0.47–0.75)
GLP-1RA + SGLT2ivs SGLT2i monotherapyMI
0.73(0.61–0.88)
GLP-1RA + SGLT2ivs SGLT2i monotherapystroke
0.72(0.53–0.97)
GLP-1RA + SGLT2ivs SGLT2i monotherapyall-cause mortality
0.57(0.48–0.67)
GLP-1RA + SGLT2ivs SGLT2i monotherapyHF hospitalization/events
0.71(0.59–0.86)
GLP-1RA + SGLT2ivs GLP-1RA monotherapyCV mortality
0.35(0.15–0.81)
GLP-1RA + SGLT2ivs GLP-1RA monotherapyMI
0.93(0.88–0.97)
GLP-1RA + SGLT2ivs GLP-1RA monotherapystroke
0.92(0.88–0.96)
GLP-1RA + SGLT2ivs GLP-1RA monotherapyall-cause mortality
0.59(0.49–0.70)
GLP-1RA + SGLT2ivs GLP-1RA monotherapyHF hospitalization/events
0.84(0.81–0.88)
GLP-1RA + SGLT2ivs GLP-1RA monotherapyserious renal events
0.43(0.23–0.80)
Further pooled results
RCTs: GLP-1 RA effect by baseline SGLT2i use (interaction)
- Major adverse cardiac events (MACE), P for interaction
- P = 0.730
- Cardiovascular (CV) mortality, P for interaction
- P = 0.889
- Non-fatal myocardial infarction (MI), P for interaction
- P = 0.237
- Non-fatal stroke, P for interaction
- P = 0.696
- All-cause mortality, P for interaction
- P = 0.682
- Heart failure (HF) hospitalization, P for interaction
- P = 0.257
- Renal composite outcome, P for interaction
- P = 0.890
- Consistent GLP-1 RA reduction in outcomes irrespective of baseline SGLT2i use
Original publication
Cardiovascular and renal outcomes of dual combination therapies with glucagon-like peptide-1 receptor agonists and sodium-glucose transport protein 2 inhibitors: a systematic review and meta-analysis. Cardiovasc Diabetol. Published 30 September 2025. doi:10.
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