Cardiovascular and renal outcomes of combined SGLT2 inhibitors and GLP-1 receptor agonists versus monotherapy in patients with type 2 diabetes mellitus: a network meta-analysis
Abstract
Background: Whether using both sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) is more effective than using either alone in type 2 diabetes mellitus remains uncertain. We sought to assess cardiovascular and kidney outcomes of combined SGLT2i and GLP-1RA therapy versus monotherapy using network meta-analysis.
Methods: We identified randomized controlled trials (RCTs) of SGLT2i or GLP-1RA in patients with type 2 diabetes mellitus through a comprehensive search of MEDLINE, Embase, and the Cochrane Library until Aug. 15, 2025. We compared patients receiving SGLT2i, GLP-1RA, both SGLT2i and GLP-1RA, or neither medication in a systematic review and network meta-analysis. Primary outcomes were major adverse cardiovascular events (cardiovascular death, myocardial infarction, and stroke) and major adverse kidney events (decline in estimated glomerular filtration rate, kidney failure, and death due to kidney failure). Secondary outcomes included heart failure-related hospital admissions, serious adverse events, and hypoglycemia.
Results: We included 12 RCTs with 99 683 participants. The risk of major adverse cardiovascular events did not differ significantly with combined SGLT2i and GLP-1RA therapy compared with SGLT2i (risk ratio [RR] 0.86, 95% confidence interval [CI] 0.74 to 1.01; very low certainty) or GLP-1RA alone (RR 0.95, 95% CI 0.81 to 1.12; very low certainty). Similarly, the risk of major adverse kidney events did…
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: 99 participants or records.
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