Key result
Incretin therapies improve KCCQ clinical summary scores by ~7 points vs placebo in obesity-related HFpEF.
Why the study?
Direct comparative evidence between incretin-based therapies and sodium-glucose cotransporter 2 inhibitors in obesity-related HFpEF was lacking.
Do incretin-based therapies and SGLT2 inhibitors improve patient-reported health status and functional capacity in obesity-related heart failure with preserved ejection fraction compared to placebo?
Meta-Analysis
Do incretin-based therapies and SGLT2 inhibitors improve patient-reported health status and functional capacity in obesity-related heart failure with preserved ejection fraction compared to placebo?
Incretin-based therapies provide consistent, clinically meaningful improvements in patient-reported health status and functional capacity in obesity-related HFpEF, whereas SGLT2 inhibitor data in this specific phenotype are more heterogeneous and indirect.
Answers are grounded in this paper and cite their sources.
Supports incretin therapies to improve health status in obesity-related HFpEF; confirms consistent benefits across randomized programmes.
Background: Obesity-related heart failure with preserved ejection fraction is characterised by symptom burden, impaired mobility, and reduced health status. Direct comparative evidence between incretin-based therapies and sodium-glucose cotransporter 2 inhibitors is lacking. Methods: We conducted a PRISMA-guided systematic review and programme-level meta-analysis, using the independent parent randomised trial programme as the unit of analysis to avoid double-counting linked reports. The primary endpoint was the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, and the secondary endpoint was the six-minute walk distance. Random-effects models used restricted maximum likelihood estimation with Knapp-Hartung inference. Results: Six parent programmes were included: STEP-heart failure with preserved ejection fraction, STEP-heart failure with preserved ejection fraction DM, SUMMIT, PRESERVED-HF, EMPEROR-Preserved, and DELIVER. In obesity-focused incretin programmes, pooled mean differences were 7.38 Kansas City Cardiomyopathy Questionnaire Clinical Summary Score points (95% confidence interval, 6.29 to 8.48; I 2 = 0.00%) and 17.60 m for six-minute walk distance (95% confidence interval, 10.69 to 24.52; I 2 = 0.00%). The secondary sodium-glucose cotransporter 2 Kansas City Cardiomyopathy Questionnaire Clinical Summary Score synthesis showed a pooled mean difference of 2.53 points (95% confidence interval, −1.97 to 7.03; I 2 = 82.21%). No parent programme was judged to be at high risk of bias. Conclusions: Incretin-based therapies showed consistent patient-centred improvements in obesity-related heart failure with preserved ejection fraction, whereas sodium-glucose cotransporter 2 inhibitor evidence was derived from broader heart failure with mildly reduced ejection fraction/heart failure with preserved ejection fraction populations and was more heterogeneous. Cross-class comparisons remain exploratory because of population differences, follow-up differences, limited six-minute walk distance availability, and the absence of direct comparative trials; these findings do not establish class superiority.
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Khan et al. (2026) conducted a meta-analysis in Obesity-related heart failure with preserved ejection fraction. Incretin-based therapies vs. Placebo was evaluated on Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) (MD 7.38, 95% CI 6.29 to 8.48). Incretin-based therapies improved the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score by a pooled mean difference of 7.38 points compared to placebo in obesity-related HFpEF.
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