Glucagon-like peptide-1-based incretin agonists in obesity-related heart failure with preserved ejection fraction: A systematic review and meta-analysis

Figure 2 Risk of bias assessment of included randomized controlled trials using the Cochrane Risk of Bias 2 tool across five domains: D1, randomization process; D2, deviations from intended interventions; D3, missing outcome data; D4, measurement of the outcome; D5, selection of the reported result. All three trials were rated low risk for D1, D3, and D5. Some concerns were assigned for D2 and D4 across all trials, owing to the potential for functional unblinding: The characteristic gastrointestinal side effects and substantial visible weight loss associated with glucagon-like peptide-1-based therapy may allow participants to infer treatment allocation, potentially influencing the patient-reported Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) outcome. The SUMMIT trial additionally carries some concerns for D2 due to higher drug discontinuation related to gastrointestinal adverse effects (6.3% vs 1.4% with placebo). Overall risk of bias was rated some concerns for all three trials. D2 and D4: Some Concerns due to potential functional unblinding-KCCQ-CSS is patient-reported and visible weight loss/GI side effects may allow participants to infer treatment allocation. HFpEF: Heart failure with preserved ejection fraction.