Objective: To investigate an effect of sodium glucose linked transporter 2 (SGLT2) inhibitor dapagliflosin on the levels of adropin in patients with type 2 diabetes mellitus (T2DM) with chronic heart failure (HF). Design and method: The study is open label multicenter (private hospital Vita-Centre, Zaporozhye, Ukraine, EliteMedService, Zaporozhye, Ukraine and City Hospital #7, Zaporozhye, Ukraine) non-randomized cohort investigation. We prospectively enrolled 417 patients with T2DM and HF from entire cohort of 612 T2DM pa-tients. The eligible patients were treated with guided-recommended HF therapy de-pending on HF phenotypes, which included SGLT2 inhibitor dapagliflozin in a dose of 10 mg OD orally along with angiotensin receptor-neprilysin inhibitor (ARNI) / ACE inhibitors / angiotensin-II receptor blockers (ARBs), mineralocorticoid receptor antag-onist (MRA), beta-blockers. Anthropometrics, clinical data, Echocardiography / Doppler examinations and biomarkers assessments were performed at the baseline and over 6-month interval. Results: Over 6-month period after initial prescription of SGLT2 inhibitor dapagliflozin the levels of adropin in entire group demonstrated a significant growth up to 26.6% (from 237.4 [25%-75% IQR = 190.50–275.30] ng/mL to 300.2 [25%-75% IQR = 267.80–335.70] ng/mL, P = 0.04). In female subgroup, an increase in circulating level of adropin was sufficiently higher (from 269.5 [25%-75% IQR = 231.20–299.20] ng/mL to 365.2 [25%-75% IQR = 340.10–388.60] ng/mL, P = 0.01), when com-pared with male subgroup (from 211.2 [25%-75% IQR = 190.40–237.50] ng/mL to 259.6 [25%-75% IQR = 206.50–321.40] ng/mL, P = 0.16). Multivariate logistic regression analysis of entire group showed that relative changes of left ventricular (LV) ejection fraction (LVEF), left atrial volume index (LAVI), and E/e` were significantly associated with increased adropin levels. In fe-male subgroup, but not in male subgroup, relative changes of LVEF (P = 0.046), LAVI (P = 0.001) and E/e` (P = 0.001) exhibited their independent predictive values for adropin changes. Conclusions: The levels of adropin seem to be a predictor for favorable modification of hemodynamic perfor-mances that is independent from N-terminal brain natriuretic pro-peptide.