Effects of new hypoglycemic drugs on cardiac remodeling: a systematic review and network meta-analysis

Background: In recent years, the incidence of diabetes mellitus has been increasing annually and cardiovascular complications secondary to diabetes mellitus have become the main cause of death in diabetic patients. Although some novel glucose-lowering drugs have been shown to be cardioprotective, it is unclear which glucose-lowering drugs are effective in improving cardiac remodeling and fundamentally delay the progression of heart failure. The purpose of this network meta-analysis was to compare the effects of sodium glucose cotransporter type 2 inhibitor (SGLT-2i), glucagon-like peptide 1 receptor agonist (GLP-1RA) and dipeptidyl peptidase-4 inhibitor (DPP-4i) on ventricular remodeling in patients with type 2 diabetes (T2DM) and/or cardiovascular disease (CVD). Methods: Articles published prior to 24 August 2022 were retrieved in four electronic databases: PubMed, EMBASE, Cochrane Library, and Web of Science. We included randomized controlled trials (RCTs) and a small cohort study in this meta-analysis. The differences of mean changes of left ventricular ultrasonic parameters between the treatment group and the control group were compared. Results: A total of 31 RCTs and 4 cohort studies involving 4322 patients were analyzed. SGLT-2i had significantly reduced left ventricular end-diastolic diameter (LVEDD) [MD=-0.72ml, 95% CI (-1.30, -0.14)] and LV mass index (LVMI) [MD=-0.28g/m 2 , 95% CI (-0.43, -0.12)]. GLP-1RA had significantly reduced LV end-systolic diameter (LVESD) [MD=-0.38mm, 95% CI (-0.66, -0.10)], LVMI [MD=-1.07g/m 2 , 95% CI (-1.71, -0.42)], and e' [MD=-0.43cm/s 95% CI (-0.81, -0.04)]. DPP-4i significantly improved e' [MD=3.82cm/s, 95%CI (2.92,4.7)] and E/e' [MD = -5.97 95% CI (-10.35, -1.59)], but decreased LV ejection fraction (LVEF) [MD = -0.89% 95% CI (-1.76, -0.03)]. Conculusion GLP-1RA were more significantly associated with improvement in LVESD and LVMI, but significantly decreased e'. DPP-4i were more strongly associated with improvement in e' and E/e', but significantly inhibited LVEF. SGLT-2i significantly improved LVMI and LVEDD in the overall population, as well as E/e' and SBP in T2DM patients combined with CVD, without showing any negative effect on left ventricular function. Therefore, we recommend SGLT-2i as the most effective drug for reversing ventricular remodeling.