Larger effect size in composite kidney outcomes than in major cardiovascular events associated with sodium‐glucose cotransporter‐2 ( SGLT2) inhibitors compared with glucagon‐like peptide‐1 receptor agonists ( GLP ‐1 RAs) : A pooled analysis of type 2 diabetes trials
Authors' conclusion
In T2D patients, treatment effect sizes were greater for kidney than for macrovascular (MACE-3) outcomes, with important differences according to the drugs considered. CKO and MACE-3 are independent. Caution must be taken when interpreting CKO in the absence of MACE-3 data.
Study context
- Population
- Patients with T2D in placebo-controlled Phase 3 trials of glucose-lowering interventions reporting composite kidney outcome (CKO) and major adverse cardiovascular event (MACE-3) (MEDLINE to December 31, 2021)
- Participants
- 104,987 patients12 studies
- Comparison
- Treatment effect size on composite kidney outcome (CKO) vs MACE-3 with SGLT2 inhibitors and GLP-1 RAs
- Outcome
- Ratio of hazard ratios (HRs) (rHR): HR for CKO to HR for MACE-3
Methodological detailsplacebo-controlled Phase 3 trials, random-effects meta-analysis, weighted meta-regression
- Placebo-controlled Phase 3 trials
- Random-effects meta-analysis
- Weighted meta-regression
Pooled result
As reported in the abstract
rHR (CKO vs MACE-3)
Treatment effect sizes 17% greater for CKO than for MACE-3, especially for SGLT2 inhibitor trials vs GLP-1 RAs; Ratio of HRs (rHR)
0.83 (0.74 to 0.92); I2 = 50%; P = 0.03; τ2 = 0.0161 (95% CI)
Further pooled results
Effect size greater for CKO than for individual CV outcomes
- vs MI
- 22%
- vs stroke
- 21%
- vs death from CV causes
- 16%
- vs hospitalization for heart disease
- 9%
Correlation between MACE-3 and CKO effects
- Moderate correlation (ρ)
- 0.40; P = 0.21
- Variability in MACE-3 effect explained by CKO effect (R2), 95% CI
- 11% (1% to 54%)
- Weighted meta-regression
Original publication
Larger effect size in composite kidney outcomes than in major cardiovascular events associated with sodium‐glucose cotransporter‐2 ( SGLT2) inhibitors compared with glucagon‐like peptide‐1 receptor agonists ( GLP ‐1 RAs) : A pooled analysis of type 2 diabetes trials. Diabetes Obes Metab. Published 23 September 2022. doi:10.
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