title: Antidiabetic agents: Potential anti-inflammatory activity beyond glucose control.
abstract: A growing body of evidence is emerging to show that abdominal obesity, the metabolic syndrome, type 2 diabetes, cardiovascular disease and microvascular diabetic complications are intimately related to chronic inflammation. These observations pave the way to the development of new pharmacological strategies that aim to reduce silent inflammation. However, besides specific anti-inflammatory agents, glucose-lowering medications may also exert anti-inflammatory effects that could contribute to improved outcomes in diabetic patients. Most studies have used metformin, an AMP-activated protein kinase (AMPK) activator, and thiazolidinediones (TZDs), which act as peroxisome proliferator-activated receptor-gamma (PPARγ) agonists. Both pharmacological classes (considered insulin-sparing agents or insulin sensitizers) appear to have greater anti-inflammatory activity than insulin-secreting agents such as sulphonylureas or glinides. In particular, TZDs have shown the widest range of evidence of lowered tissue (visceral fat and liver) and serum inflammation. In contrast, despite reducing postprandial hyperglycaemia, the effect of α-glucosidase inhibitors on inflammatory markers appears rather modest, whereas dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) and glucagon-like peptide-1 (GLP-1) receptor agonists appear more promising in this respect. These incretin-based therapies exert pleiotropic effects, including reports of anti-inflammatory activity. No human data are available so far regarding sodium-glucose cotransporter type 2 (SGLT2) inhibitors. Although they may have indirect effects due to reduced glucotoxicity, their specific mode of action in the kidneys does not suggest systemic anti-inflammatory activity. Also, in spite of the complex relationship between insulin and atherosclerosis, exogenous insulin may also exert anti-inflammatory effects. Nevertheless, for all these glucose-lowering agents, it is essential to distinguish between anti-inflammatory effects resulting from better glucose control and potential anti-inflammatory effects related to intrinsic actions of the pharmacological class. Finally, it would also be of major clinical interest to define what role the anti-inflammatory effects of these glucose-lowering agents may play in the prevention of macrovascular and microvascular diabetic complications.
authors: Clinical Pharmacology Unit, Center for Interdisciplinary Research on Medicines (CIRM), University of Liège and Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU de Liège, CHU Sart Tilman (B35), 4000 Liège 1, Belgium. Electronic address: andre.scheen@chu.ulg.ac.be.
authors: A J
authors: AJ
authors: Scheen
authors: Diabetology and Nutrition Unit, GIGA-I3, University of Liege, and Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU de Liège, Liège, Belgium.
authors: N
authors: N
authors: Esser
authors: Diabetology and Nutrition Unit, GIGA-I3, University of Liege, and Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU de Liège, Liège, Belgium.
authors: N
authors: N
authors: Paquot
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents; D001786:Blood Glucose / Q000187:drug effects / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D007004:Hypoglycemic Agents; D007249:Inflammation / Q000503:physiopathology*; D024821:Metabolic Syndrome; D051379:Mice; D009765:Obesity; D051381:Rats
chemical_list: D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; D007004:Hypoglycemic Agents
keywords: GLP-1 receptor agonist; Gliptin; Inflammation; Metformin; Thiazolidinedione; Type 2 diabetes mellitus