SGLT2 Inhibitors in Patients with Heart Failure: A Model-Based Meta-Analysis

This study aimed to quantify the effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on N-terminal pro-B-type natriuretic peptide (NT-proBNP) as a therapeutic approach for heart failure.

A systematic literature review was conducted to collect pharmacokinetics (PK) and pharmacodynamics (PD) data on empagliflozin, dapagliflozin, and canagliflozin. Population pharmacokinetic models were developed separately for each drug, along with PK/PD turnover models for SGLT2 inhibitors, to describe the time course of NT-proBNP and simulate its changes over 52 weeks.

A total of 42 publications were included in this study. The results showed that baseline NT-proBNP levels, estimated glomerular filtration rate levels, and body weight significantly influenced the therapeutic effects of SGLT2 inhibitors. Among the studied drugs, canagliflozin demonstrated a greater reduction in NT-proBNP at comparable baseline levels.

Baseline NT-proBNP concentration, renal function, and body weight were covariates affecting the efficacy of SGLT2 inhibitors in reducing NT-proBNP. Canagliflozin showed the most favorable treatment outcomes at similar baseline levels. This model-based meta-analysis approach may support further drug development for SGLT2 inhibitors.