Efficacy and safety of SGLT2 inhibitors with and without glucagon-like peptide 1 receptor agonists: a SMART-C collaborative meta-analysis of randomised controlled trials
An erratum to this article was published (Lancet Diabetes Endocrinol, Jul 2026 ↗)
Authors' conclusion
The effects of SGLT2 inhibitors on cardiovascular and kidney outcomes are consistent regardless of the background use of GLP-1 receptor agonists. These findings suggest independent effects of these evidence-based therapies and support clinical practice guidelines recommending the use of these agents in combination to improve cardiovascular and kidney metabolic outcomes.
Study context
- Population
- Participants with diabetes in SGLT2i vs placebo trials of the SGLT2 Inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium
- Participants
- 73,238 participants12 RCTs
- Comparison
- SGLT2i vs placebo, by background GLP-1 RA use
- Outcome
- MACE (nonfatal MI, nonfatal stroke or cardiovascular death); hospitalisation for HF or cardiovascular death
Methodological detailscollaborative meta-analysis, SMART-C consortium, double-blind, placebo-controlled trials, inverse variance weighted
- Collaborative meta-analysis
- SMART-C consortium
- Double-blind, placebo-controlled trials
- Inverse variance weighted
Pooled result
As reported in the abstract
Main CV outcomes by background GLP-1 receptor agonist use
SGLT2 inhibitors vs PlaceboHazard ratio (95% CI)P value
MACE; participants receiving GLP-1 receptor agonists
0.81(0.63–1.03)
P = 0.31for heterogeneityMACE; participants not receiving GLP-1 receptor agonists
0.90(0.86–0.94)
P = 0.31for heterogeneityHF hospitalisation or CV death; with GLP-1 receptor agonist use
0.76(0.57–1.01)
P = 0.90for heterogeneityHF hospitalisation or CV death; without GLP-1 receptor agonist use
0.78(0.74–0.82)
P = 0.90for heterogeneityFurther pooled results
| Outcome | HR (CI) | P value | |
|---|---|---|---|
| CKD progression by GLP-1 receptor agonist useSGLT2 inhibitorsvs PlaceboWith GLP-1 receptor agonist use | 0.65 (0.46–0.94) | P for heterogeneity = 0.81 | |
| CKD progression by GLP-1 receptor agonist useSGLT2 inhibitorsvs PlaceboWithout GLP-1 receptor agonist use | 0.67 (0.62–0.72) | P for heterogeneity = 0.81 | |
| 0.512Hazard ratio (log scale) |
Chronic rate of change in eGFR over time by GLP-1 receptor agonist use
- Effect consistent regardless of GLP-1 receptor agonist use (heterogeneity)
- 0.92
Safety
| Outcome | RR (95% CI) | P value | |
|---|---|---|---|
| Serious adverse events by GLP-1 receptor agonist useSGLT2 inhibitorsvs PlaceboWith GLP-1 receptor agonist use | 0.87 (0.79–0.96) | P for heterogeneity = 0.41 | |
| Serious adverse events by GLP-1 receptor agonist useSGLT2 inhibitorsvs PlaceboWithout GLP-1 receptor agonist use | 0.91 (0.89–0.93) | P for heterogeneity = 0.41 | |
| 0.512Relative risk (log scale) |
Serious adverse events by GLP-1 receptor agonist use
- Fewer serious adverse events with SGLT2 inhibitors vs placebo, irrespective of GLP-1 receptor agonist use
Original publication
Efficacy and safety of SGLT2 inhibitors with and without glucagon-like peptide 1 receptor agonists: a SMART-C collaborative meta-analysis of randomised controlled trials. Lancet Diabetes Endocrinol. Published 8 July 2024. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →