BACKGROUND: Patients treated with GLP-1 receptor agonists and SGLT2 inhibitors often have underlying conditions that predispose them to infection. While these agents offer cardiometabolic benefits, concerns persist regarding their impact on infectious risk. Existing literature has not comprehensively assessed their dose-dependent influence on severe infections such as sepsis.
OBJECTIVES: To investigate the effect of GLP-1 receptor agonists and SGLT2 inhibitors on infection risk.
DATA SOURCES: PubMed, Embase, ClinicalKey, Cochrane CENTRAL, ProQuest, ScienceDirect, Web of Science, and ClinicalTrials.gov up to December 18, 2024.
STUDY ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) reporting target infection outcomes related to GLP-1 receptor agonists or SGLT2 inhibitors prescription.
PARTICIPANTS: Individuals without evidence of ongoing infection at study initiation.
INTERVENTIONS: GLP-1 receptor agonists or SGLT2 inhibitors ASSESSMENT OF RISK OF BIAS: Cochrane Risk of Bias Tool version 2.0 METHODS OF DATA SYNTHESIS: A frequentist random-effects model was used to assess the comparative incidence of infectious complications-classified as sepsis, abscess/gangrene, or other infections (e.g., pneumonia, UTI). Drop-out rates served to reflect acceptability. Sensitivity analyses included Bayesian modeling and subgroup analyses of diabetic status and treatment duration.
RESULTS: Based on 105 RCTs with 219,283 participants, no significant association was found between GLP-1 receptor agonists or SGLT2 inhibitors and controls, except for high-dose canagliflozin (300 mg/day), which was the only intervention significantly associated with reduced sepsis risk versus control. This effect persisted in participants with diabetes. No significant associations were found between any other GLP-1 receptor agonist or SGLT2 inhibitor and risk of sepsis, abscess, gangrene, or other infections. Subgroup and meta-regression analyses confirmed robustness. Bayesian modeling yielded comparable results. Treatment duration had minimal influence on primary outcomes.
CONCLUSIONS: This analysis identifies no significant evidence of infection-related adverse events related to GLP-1 receptor agonist or SGLT2 inhibitors prescription.
TRIAL REGISTRATION: PROSPERO CRD42024628901.
