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-1RAs): A pooled analysis of type 2 diabetes trials
Abstract
Aim: To compare treatment effect sizes between a composite kidney outcome (CKO) and three-point major adverse cardiovascular event (MACE-3) outcomes with use of sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs), and to investigate the relationship between treatment effects on CKO and MACE-3 in patients with type 2 diabetes (T2D).
Materials and methods: We performed a MEDLINE database search up to December 31, 2021 to identify all placebo-controlled Phase 3 trials which investigated the efficacy of glucose-lowering interventions, and selected those reporting results for CKO and MACE-3. Hazard ratios (HRs) with 95% confidence intervals (CIs) for both outcomes were extracted for each trial, and we evaluated differences in treatment effect sizes by using a ratio of HRs (rHR): the HR for CKO to the HR for MACE-3. A random-effects meta-analysis was used to obtain the overall rHR across trials and according to subgroup. We investigated the relationship between treatment effects on CKO and MACE-3 using the coefficient of determination (R2 ) with weighted meta-regression. The study protocol was registered on PROSPERO (CRD42022299690).
Results: A total of 12 studies fulfilled the prespecified criteria, and comprised a total of 104 987 patients with T2D. On average, treatment effect sizes were 17% greater for CKO than for MACE-3 (rHR 0.83, 95% CI 0.74 to 0.92; I2 = 50%; P = 0.03; τ2 = 0.0161), especially for trials of SGLT2…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 104 participants or records.
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