Short-term changes in NT-proBNP levels following initiation of SGLT2 inhibitors or GLP-1 receptor agonists in patients with type 2 diabetes and heart stress

Prevention in type 2 diabetes (T2DM) relies on identifying subclinical organ damage. This study examined the “Heart Stress” (HS) phenotype—defined by the Heart Failure Association-European Society of Cardiology (HFA-ESC) as asymptomatic elevated N-terminal pro-brain natriuretic peptide (NT-proBNP), irrespective of the presence or absence of detectable structural cardiac abnormalities. We investigated early NT-proBNP trajectories following initiation of SGLT2 inhibitors (SGLT2i) or GLP-1 receptor agonists (GLP-1 RA) in a multicenter, longitudinal study involving 100 T2DM outpatients meeting HS criteria (baseline median NT-proBNP 192.5 pg/mL). Together with the analysis on raw NT-proBNP levels, NT-proBNP were further adjusted for age, estimated glomerular filtration rate (eGFR), and body mass index (BMI) at baseline and after 3 months in a secondary analysis to account for the known influence of renal function changes and weight loss on circulating NT-proBNP concentrations. Overall, the mean age was 73.3 ± 7.7 years. After a 3-month follow-up, we found no significant changes in raw NT-proBNP levels in either group. An interaction was present between raw NT-proBNP trajectory and ΔeGFR ( p for interaction = 0.012) in the SGLT2i group, with significant reduction of − 6.4% (95% CI − 11.9% to − 0.8%, p = 0.026) in the lowest ΔeGFR tertile. Considering adjusted NT-proBNP, the SGLT2i group showed a modest reduction (− 2.4%, 95% CI − 4.7% to − 0.2%, p = 0.035), whereas younger patients (< 70 years) had a more robust decrease (− 9.0%, 95% CI − 13.4% to − 4.6%, p < 0.001). An interaction between ΔBMI, as a continuous variable, and raw NT-proBNP trajectory was found in the GLP-1 RA group ( p for interaction = 0.027). The GLP-1 RA group showed a − 6.5% reduction (95% CI − 10.4% to − 2.4%, p = 0.002), with the most significant drop (− 13.0%, 95% CI − 20.6% to − 4.7%, p = 0.002) in those with the highest baseline adjusted NT-proBNP levels. In conclusion, early intervention with SGLT2i and GLP-1 RA was associated with modest short-term changes in NT-proBNP trajectories among T2DM patients with HS. These findings suggest that NT-proBNP may provide useful information for characterizing early cardiometabolic risk profiles, although the clinical significance of the short-term observed changes requires further investigation.