Introduction: SGLT2 inhibitors reduce cardiovascular (CV) risk in a broad range of patients including those with and without type 2 diabetes mellitus (DM). In addition, non-glycemic effects modify parameters that define metabolic syndrome (MetS) such as weight, BP, and lipid profile. In this context, we investigated the effects of dapagliflozin on key components of MetS and the association with outcomes. Methods: 17,160 patients with DM were randomized to dapagliflozin or placebo in DECLARE-TIMI 58. Since all had DM, MetS was classified using a modification of IDF criteria requiring BMI ≥30 kg/m 2 and ≥1 of the following: triglycerides ≥150 mg/dL, HDL-C <40 in men or <50 mg/dL in women, SBP ≥130 or DBP ≥85 mmHg. Classification of MetS and its subcomponents were tracked at baseline and follow-up visits (6-48 months). An analysis adjusted for baseline characteristics and treatment was performed to assess the association of MetS with key outcomes. Results: At baseline, 53% had MetS. On adjusted analysis, MetS was predictive of CV death or hospitalization for heart failure (CVD/HHF) (HR 1.28, 95%CI 1.11-1.47, p<0.001), HHF (HR 1.62, 95%CI 1.33-1.97, p<0.001), and MI (HR 1.22, 95%CI 1.05-1.4, p=0.008). From 6 to 48 months, there was a lower prevalence of MetS in the dapagliflozin arm (47.9% vs. 52.5%, p<0.001, Figure 1), as well as lower prevalence of BMI ≥30 kg/m 2 (54.9% vs. 58.0%), low HDL-C (38.7% vs. 42.6%), and elevated BP (58.2% vs. 65.7%) with p<0.001 for each. In the dapagliflozin arm, there were lower odds of progression to MetS (10.5% vs. 13.5%; OR 0.76, 95%CI 0.64-0.89, p<0.001) and, in those with MetS at baseline, higher odds of regression (24.6% vs. 18.3%; OR 1.45, 95%CI 1.29-1.64, p<0.001) at 48 months. Conclusions: The presence of MetS is prognostically important in patients with DM. Dapagliflozin led to significant early and sustained changes in the likelihood of MetS.