Effects of semaglutide and dapagliflozin on natriuretic peptides in type 2 diabetes: a randomized comparative study
Abstract
Type 2 diabetes (T2D) is associated with a substantially increased risk of heart failure, partly mediated by myocardial stress and neurohormonal activation. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) both improve cardiovascular outcomes in T2D, but their comparative effects on heart failure and cardiac stress pathways remain incompletely understood. To compare the longitudinal effects of the GLP-1 RA semaglutide and the SGLT2i dapagliflozin on plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations in patients with T2D. NT-proBNP is a well-established biomarker of myocardial wall stress and prognostic risk. Post hoc analysis of a prospective, open-label randomised clinical trial that recruited participants between 2020 and 2022 and followed them for 6 months. NT-proBNP was measured in blood samples collected at baseline and after 6 months. Participants with type 2 diabetes on metformin monotherapy, recruited at a single centre, were randomised in a 1:1 ratio to treatment with semaglutide or dapagliflozin. Changes over time in NT-proBNP were analysed using Tobit regression to account for left-censoring. Between-group differences were assessed using mixed-effects models adjusted for relevant covariates. A total of 75 participants received semaglutide and 92 received dapagliflozin (mean age 66 years; 31% women; mean HbA1c 53 mmol/mol). Baseline NT-proBNP levels were overall low (median 77 ng/L, interquartile range 55–138) and below the limit of quantification in 25% of participants. During the 6-month follow-up, NT-proBNP declined significantly by 7% in the semaglutide group (p=0.01), whereas it increased by 20% in the dapagliflozin group (p=0.07). A significant time-by-treatment interaction was observed, indicating that the magnitude of change in NT-proBNP differed between the treatment groups. In patients with T2D without heart failure, treatment with semaglutide but not dapagliflozin was associated with a reduction in NT-proBNP over 6 months, independent of renal function, body mass index, and other known determinants of NT-proBNP. These findings suggest that glucose-lowering therapies may exert distinct influences on myocardial stress pathways, with potential implications for heart failure risk modulation.NT-proBNP levels at baseline and follow-up.Longitudinal trajectories by treatment group.