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
Across 12 major trials, SGLT2 inhibitors delivered the same reductions in cardiovascular and kidney events whether or not patients were already taking a GLP-1 receptor agonist — evidence that the two drug classes act independently and can be used together in high-risk diabetes.
Background
SGLT2 inhibitors and GLP-1 receptor agonists both improve cardiovascular and kidney outcomes in type 2 diabetes, but whether SGLT2-inhibitor benefits persist in patients already treated with a GLP-1 receptor agonist was uncertain.
Study design
A collaborative meta-analysis of 12 randomised, double-blind, placebo-controlled SGLT2-inhibitor trials in the SMART-C consortium, restricted to 73,238 participants with diabetes, of whom 3,065 (4.2%) were taking a GLP-1 receptor agonist at baseline; treatment effects were pooled by inverse-variance-weighted meta-analysis.
Key findings
SGLT2-inhibitor effects were consistent regardless of GLP-1 receptor agonist use for major adverse cardiovascular events, for hospitalisation for heart failure or cardiovascular death (HR 0.76 vs 0.78), and for CKD progression (HR 0.65 vs 0.67), with no significant heterogeneity. Fewer serious adverse events occurred with SGLT2 inhibitors irrespective of GLP-1 receptor agonist use.
Clinical implications
The results support the independent, complementary action of the two classes and reinforce recommendations to use them in combination for cardio-renal protection in type 2 diabetes.
Category
Research
Source
The Lancet Diabetes & Endocrinology
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