Targeting the DPP-4-GLP-1 pathway improves exercise tolerance in heart failure patients: a systematic review and meta-analysis

Abstract

BackgroundThe most significant manifestation of heart failure is exercise intolerance. This systematic review and meta-analysis was performed to investigate whether dipeptidyl peptidase-4 (DPP-4) inhibitors or glucagon-like peptide 1 receptor agonists (GLP-1 RAs), widely used anti-diabetic drugs, could improve exercise tolerance in heart failure patients with or without type 2 diabetes mellitus.MethodsAn electronic search of PubMed, EMBASE and the Cochrane Library was carried out through March 8th, 2019, for eligible trials. Only randomized controlled studies were included. The primary outcome was exercise tolerance [6-min walk test (6MWT) and peak O2 consumption], and the secondary outcomes included quality of life (QoL), adverse events (AEs) and all-cause death.ResultAfter the literature was screened by two reviewers independently, four trials (659 patients) conducted with heart failure patients with or without type 2 diabetes met the eligibility criteria. The results suggested that targeting the DPP-4-GLP-1 pathway can improve exercise tolerance in heart failure patients [MD 24.88 (95% CI 5.45, 44.31), P = 0.01] without decreasing QoL [SMD -0.51 (95% CI -1.13, 0.10), P = 0.10]; additionally, targeting the DPP-4-GLP-1 pathway did not show signs of increasing the incidence of serious AEs or mortality.ConclusionOur results suggest that DPP-4 inhibitors or GLP-1 RAs improve exercise tolerance in heart failure patients. Although the use of these drugs for heart failure has not been approved by any organization, they may be a better choice for type 2 diabetes mellitus patients with heart failure. Furthermore, as this pathway contributes to the improvement of exercise tolerance, it may be worth further investigation in exercise-intolerant patients with other diseases.

Patients With Type 2 Diabetes Mellitus and Heart Failure Benefit More From Sodium-Glucose Cotransporter 2 Inhibitor: A Systematic Review and Meta-Analysis

“…Recent studies have reported that some antidiabetes drugs may have beneficial effects in HF, including dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and SGLT-2 inhibitors. Our previous meta-analysis demonstrated that DPP-4 inhibitor and GLP-1 Ras may help improve exercise capacity in HF patients with or without diabetes (29), but these trials showed no improvement in LVEF (30)(31)(32), except in a trial with a small sample size (33). SGLT-2 inhibitors may be the most promising choice among these three kinds of drugs detailed above, according to recent meta-analyses (34)(35)(36)(37).…”

Impact of novel glucose‐lowering therapies on physical function in people with type 2 diabetes: A systematic review and meta‐analysis of randomised placebo‐controlled trials

“…to better exercise tolerance. 28 The implications of these mechanisms for physical function, however, again remain unexplored.…”

“…Dipeptidyl peptidase‐4 inhibitors (DPP4i) act via the same incretin pathway as GLP‐1RAs to improve glycaemic control 26 . Although these have failed to demonstrate the same level of cardiometabolic and weight‐lowering benefits as GLP‐1RA, there is evidence that these agents might improve oxygen consumption by the muscles and mitochondrial biogenesis through the GLP‐1 signalling pathway, 27 translating to better exercise tolerance 28 . The implications of these mechanisms for physical function, however, again remain unexplored.…”

CD14, CD163, and CCR1 are involved in heart and blood communication in ischemic cardiac diseases

“…It is estimated that 20% to 46% of people have a lifetime risk of HF, and the incidence is increasing. 1 – 3 Many cardiac diseases eventually lead to HF. 4 Because the heart has compensatory mechanisms, patients undergo the cardiac remodeling process, which leads to changes in the ionic channel, pump, exchanger densities, and kinetics, and this results in inevitable HF.…”