Effects of new hypoglycemic drugs on patients with heart failure: a systematic review and network meta-analysis
Authors: Song Ruirui , Liu Fang , Shi Xiaojing , Sun Songtao , Chen Jun , Gao Hongmei 
Published: November 2024

Abstract

Background
Currently, there is no relevant study comparing sodium-dependent glucose transporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and dipeptidyl peptidase inhibitor (DPP4i) head to head to evaluate their comprehensive impact on heart failure patients.

Methods
We conducted a comprehensive literature search across multiple databases. Utilizing the risk of bias tool from the Cochrane Collaboration, the methodological quality of included studies was critically assessed and potential publication bias was examined via funnel plots.

Results
All results are presented as mean difference; 95% confidence interval (MD; 95% CI). The network meta-analysis indicated that in regards to left ventricular function, there is a big difference in the left ventricular ejection fraction (LVEF) of Empagliflozin 25 mg (13.64; 0.26, 27.01) compared to Canagliflozin 100 mg; and significant differences in the left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) of Dapagliflozin 10 mg (−0.76; −1.27, −0.25 and −0.95; −1.86, −0.05), Vildagliptin 50 mg (−1.05; −1.47, −0.63 and −1.12; −2.19, −0.05), and Sitagliptin 100 mg (−1.34; −2.31, −0.38 and −1.89; −3.50, −0.27) compared to Empagliflozin 10 mg. In terms of the quality of life, there are significant differences in the N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the Quality of life score of Sitagliptin 100 mg (408.08; 213.59, 602.57 and 3.74; 1.57, 5.92) compared to Dapagliflozin 5 mg. In terms of the cardiovascular outcome events, there is a significant difference in the heart failure rehospitalization rate of Dapagliflozin 10 mg (0.45; 0.25, 0.82) and Empagliflozin 10 mg (0.48; 0.28, 0.81) compared to Liraglutide 1.8 mg. Further significant differences are found in the all-cause mortality of Dapagliflozin 10 mg (0.81; 0.66, 0.98) compared to Vildagliptin 50 mg; the cardiovascular death of Albiglutide 30 mg (0.49; 0.28, 0.86) compared to Exenatide 2 mg; and the arrhythmic events of Liraglutide 1.8 mg (0.49; 0.26, 0.90) compared to Empagliflozin 10 mg. The network meta-analysis of SGLT2i, GLP-1RA, and DPP4i as a class of drugs showed that GLP-1RA is superior to SGLT2i in improving LVEF and reducing myocardial infarction/acute coronary syndrome, whereas DPP4i is superior to SGLT2i in improving LVEDV and LVESV.

Conclusions
GLP-1RA is superior to SGLT2i in improving LVEF and reducing myocardial infarction/acute coronary syndrome, whereas DPP4i is superior to SGLT2i in improving LVEDV and LVESV.
Key message What is already known on this topic—It has been confirmed that three new hypoglycemic drugs have a protective effect on the cardiovascular system. Studies have shown that sodium-dependent glucose transporter 2 inhibitors (SGLT2i) can improve cardiovascular outcomes and enhance the quality of life of heart failure patients. Currently, SGLT2i is widely used in the clinical treatment of heart failure, and related studies have shown that glucagon-like peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase inhibitor (DPP4i) also play important roles in the treatment of heart failure. What this study adds—However, there is no relevant research on whether these drugs’ clinical efficacy is dose-dependent. How this study might affect research, practice, or policy—This study included different doses of hypoglycemic drugs and used a network meta-analysis method to comprehensively evaluate the effects of three hypoglycemic drugs on heart function, quality of life, and prognosis in heart failure patients, providing a basis for clinical practice.