Differentiation of risk for major adverse cardiovascular events (MACE) from heart failure hospitalization (HHF) or kidney disease is important when selecting glucose-lowering therapy. We investigated the ability of separate MACE and HHF risk scores to 1) differentiate MACE from HHF risk; and 2) identify individuals more likely to benefit from either glucagon-like peptide-1 receptor agonists (GLP-1RAs) or sodium-glucose cotransporter-2 inhibitors (SGLT2is).We identified three trials in type 2 diabetes that reported cardiovascular outcomes stratified by Thrombolysis In Myocardial Infarction Risk Scores for MACE and HHF. Pooled placebo-arm rates of HHF, MACE, and their ratio and estimated GLP-1RA- and SGLT2i-mediated reductions in events (MACE and HHF combined) were compared across cardiovascular risk strata in the trial populations.The HHF rate was less frequent than MACE at all risk levels but increased from 18% of the MACE rate at low-intermediate HHF risk to 61% at highest HHF risk. Similarly, with increasing MACE risk, the incidence of HHF increased from 19% of the MACE incidence in those at low MACE risk to 51% in those with the highest MACE risk. Estimated GLP-1RA- and SGLT2i-mediated reductions in cardiovascular events were similar in those at low-intermediate MACE or HHF risk but tended to favor SGLT2is at higher risk levels of both scores.A greater increase in the rate of HHF relative to MACE was observed with progressively higher cardiovascular risk, regardless of the risk score applied. Consequently, SGLT2is may offer greater overall cardiovascular protection in those at highest MACE risk, not just those at highest HHF risk.