Pharmacology of dipeptidyl peptidase-4 inhibitors and its use in the management of metabolic syndrome: a comprehensive review on drug repositioning

Abstract

Objectives Despite advances in our understanding of metabolic syndrome (MetS) and the treatment of each of its components separately, currently there is no single therapy approved to manage it as a single condition. Since multi-drug treatment increases drug interactions, decreases patient compliance and increases health costs, it is important to introduce single therapies that improve all of the MetS components. Evidence acquisition We conducted a PubMed, Scopus, Google Scholar, Web of Science, US FDA, utdo.ir and clinicaltrial.gov search, gathered the most relevant preclinical and clinical studies that have been published since 2010, and discussed the beneficial effects of dipeptidyl peptidase (DPP)-4 inhibitors to prevent and treat different constituent of the MetS as a single therapy. Furthermore, the pharmacology of DPP-4 inhibitors, focusing on pharmacodynamics, pharmacokinetics, drug interactions and their side effects are also reviewed. Results DPP-4 inhibitors or gliptins are a new class of oral anti-diabetic drugs that seem safe drugs with no severe side effects, commonly GI disturbance, infection and inflammatory bowel disease. They increase mass and function of pancreatic β-cells, and insulin sensitivity in liver, muscle and adipose tissue. It has been noted that gliptin therapy decreases dyslipidemia. DPP-4 inhibitors increase fatty oxidation, and cholesterol efflux, and decrease hepatic triglyceride synthase and de novo lipogenesis. They delay gastric emptying time and lead to satiety. Besides, gliptin therapy has anti-inflammatory and anti-atherogenic impacts, and improves endothelial function and reduces vascular stiffness. Conclusion The gathered data prove the efficacy of DPP-4 inhibitors in managing MetS in some levels beyond anti-diabetic effects. This review could be a lead for designing new DPP-4 inhibitors with greatest effects on MetS in future. Introducing drugs with polypharmacologic effects could increase the patient's compliance and decrease the health cost that there is not in multi-drug therapy.

The protective effect of natural compounds against rotenone‐induced neurotoxicity

“…It has been shown to have several pharmacological activities, including anti‐inflammatory and anti‐oxidative effects. [ 92,93 ] ICA improved mitochondrial respiration through the upregulation of sirtuin‐3 (Sirt3) and PGC‐1α in PC12 cells. [ 94 ] PGC‐1α interacts with Nrf2 and binds to the Sirt3 promoter to regulate Sirt3 expression.…”

Promising influences ofScutellaria baicalensisand its two active constituents, baicalin, and baicalein, against metabolic syndrome: A review

“…upregulates the expression level of GLUT4, and translocated this transporter to skeletal and cardiac muscles cells membrane (Giannocco et al, 2013;Rameshrad, Razavi, Ferns, & Hosseinzadeh, 2019). It indicates that the inhibition of DPP-IV leads to an increase in plasma level of glucagon-like peptide-1 (GLP-1), which results in lower plasma glucose, cardioprotection, and resolution of inflammation, lipid accumulation, and appetite (Rameshrad et al, 2019;Rameshrad, Razavi, Lalau, De Broe, & Hosseinzadeh, 2020).…”

Comparative Clinical Pharmacokinetics and Pharmacodynamics of Investigational Once-Daily Sustained-Release (SR) Vildagliptin 100 mg Tablet Formulation with Conventional 50 mg Twice-Daily Regimen in Healthy Indian Males

“…Unlike, sulfonylureas and biguanides they do not cause hypoglycaemia or weight-gain complications. As a result, several DPP-4 inhibitors are currently available as a regulatory approved therapy [5][6][7]. Among the gliptins, vildagliptin is a competitive, reversible DPP-4 inhibitor [8,9].…”