Background: Prior meta-analyses suggest that the relative cardiovascular (CV) risk reduction by sodium glucose transporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) is larger in established CV disease. We investigated heterogeneity of treatment benefits along the continuum of CV risk.

Methods: We performed meta-regression analyses of CV outcome trials (9 on SGLT2i, 8 on GLP-1RAs) using log hazard ratios and CV mortality rates in the control group as proxy for baseline risk and background treatment profile of trial populations. We evaluated effects for all-cause mortality, major adverse cardiovascular events (MACE) , and heart failure. We computed absolute risk difference (ARD) in 5-year CV mortality for each trial and studied its relationship with baseline risk.

Results: We did not find statistically significant associations between baseline risk and log hazard ratios for any outcome (slope range .21; p>.10) . The ARD for 5-year CV mortality increased significantly with higher baseline risk for SGLT2i, to a predicted 2.78% in high risk (Figure) . For GLP1-RA trials, this relationship was not significant likely due to less variation in baseline risk.

Conclusion: Absolute, but not relative, CV benefits of novel diabetes drugs depend on baseline risk, which is important in guiding treatment decisions based on risk stratification.


J.M.Rodriguez-valadez: None. W.Max: None. K.Fleischmann: None. B.Ferket: None. M.Hunink: None. U.Masharani: Advisory Panel; Ryse Health, Research Support; Clementia Pharmaceuticals. J.Yeboah: None. M.Park: Advisory Panel; Otsuka America Pharmaceutical, Inc., Reata Pharmaceuticals, Inc., Other Relationship; Merck & Co., Inc. L.Li: None. E.Weber: None. Y.Li: None. A.Berkalieva: None.


Research reported in this abstract was supported by the National Heart, Lung, And Blood Institute (NHLBI) of the National Institutes of Health under award number: R01HL153456. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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