Effectiveness and safety of combining SGLT2 inhibitors and GLP-1 receptor agonists in individuals with type 2 diabetes: a systematic review and meta-analysis of cohort studies
Abstract
AIMS/HYPOTHESIS: Sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce cardiorenal risk in type 2 diabetes. However, the effect of combining these drugs remains uncertain. This systematic review aimed to evaluate the potential effectiveness and safety of combination therapy compared with monotherapy in individuals with type 2 diabetes.
METHOD: We systematically searched PubMed and Embase from inception to 1 May 2025 for cohort studies comparing the effect of combination therapy with SGLT2 inhibitor or GLP-1 RA monotherapy on (cardiovascular) mortality and cardiovascular or kidney endpoints in individuals with type 2 diabetes. Studies enrolling individuals with type 1 diabetes or a maximum follow-up of less than 1 year were excluded. The primary outcome was a composite of major adverse cardiovascular events (MACE). Secondary outcomes included all-cause mortality, cardiovascular mortality, hospitalisation for heart failure, a kidney composite endpoint and serious adverse events. Risk of bias was assessed with ROBINS-I. Risk ratios (RRs) and 95% CIs were pooled in random effects meta-analyses. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE).
RESULTS: We included 18 cohort studies (1,164,774 participants). In cohort studies, combination therapy was associated with a lower risk of MACE (RR 0.56 [95% CI 0.43, 0.71]; low certainty of evidence) and the…
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: 1,164,774 participants or records.
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