Introduction: Circulating cardiovascular (CV) biomarkers, including N-terminal pro-B type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT), are associated with risk of heart failure (HF) events in patients (pts) with type 2 diabetes (T2D). Less is known about the prognostic significance of changes in these biomarkers over time or the early effects of the SGLT2i dapagliflozin (dapa) on these markers. Methods: DECLARE-TIMI 58 was a randomized, placebo-controlled trial of dapa in 17,160 pts with T2D (median f/u = 4.2y). NT-proBNP & hsTnT (Roche) were measured at baseline & 6 mo. The outcome of interest was CV death (CVD) or hosp for HF (HHF). Outcome analyses were performed from a landmark of the 6-mo study visit with pts categorized by change in each biomarker over the first 6 mo. Hazard ratios were adjusted for baseline biomarker value, randomized treatment, age, sex, race, smoking, eGFR, prior HF, BMI, T2D duration, insulin use, CAD, prior MI, ischemic stroke, PAD, dyslipidemia, & hypertension. Linear mixed models were used to assess the effect of dapa on log-transformed NT-proBNP & hsTnT. Results: Serial NT-proBNP & hsTnT values were available in 13,459 pts (78%). Among pts allocated to placebo (n=6,698), NT-proBNP was more dynamic than hsTnT (≥20% change from baseline in 71% vs. 33% of pts; p<0.001). In the full cohort, independent of randomized treatment, there was a stepwise graded relationship between change in NT-proBNP & hsTnT and risk of CVD/HHF, whereby increases in either biomarker were associated with higher risk and decreases in either biomarker were associated with lower risk (p-trend for adj-HR <0.001 for each). Considered together, changes in the 2 markers were complementary ( Fig ; p<0.001). Dapa significantly reduced NT-proBNP (relative LS mean change, -6% [-4% to -8%]; p<0.001) but not hsTnT (0% [-1% to +1%]; p=0.92) over 6 mo. Conclusions: Early changes in hsTnT & NT-proBNP are associated with subsequent risk of CVD/HHF in pts with T2D.