Hypoglycemic agents and potential anti-inflammatory activity

Abstract

Current literature shows an association of diabetes and secondary complications with chronic inflammation. Evidence of these immunological changes include altered levels of cytokines and chemokines, changes in the numbers and activation states of various leukocyte populations, apoptosis, and fibrosis during diabetes. Therefore, treatment of diabetes and its complications may include pharmacological strategies to reduce inflammation. Apart from anti-inflammatory drugs, various hypoglycemic agents have also been found to reduce inflammation that could contribute to improved outcomes. Extensive studies have been carried out with thiazolidinediones (peroxisome proliferator-activated receptor-γ agonist), dipeptidyl peptidase-4 inhibitors, and metformin (AMP-activated protein kinase activator) with each of these classes of compounds showing moderate-to-strong anti-inflammatory action. Sulfonylureas and alpha glucosidase inhibitors appeared to exert modest effects, while the injectable agents, insulin and glucagon-like peptide-1 receptor agonists, may improve secondary complications due to their anti-inflammatory potential. Currently, there is a lack of clinical data on anti-inflammatory effects of sodium-glucose cotransporter type 2 inhibitors. Nevertheless, for all these glucose-lowering agents, it is essential to distinguish between anti-inflammatory effects resulting from better glucose control and effects related to intrinsic anti-inflammatory actions of the pharmacological class of compounds.

Keywords: diabetes; gliptin; inflammation; insulin; metformin; thiazolidinedione.

Figure 1

Impact of antidiabetic agents on inflammation. Notes: Antidiabetic drugs indirectly decrease inflammation by controlling hyperglycemia by acting on respective target tissues. Hypoglycemic agents also have direct anti-inflammatory activity independent of their effect on hyperglycemia. Abbreviations: SGLT2, sodium–glucose cotransporter type 2; GLP-1RA, glucagon like peptide-1 receptor agonist; DPP-4, dipeptidyl peptidase-4.