Figure 1 Sites of action of glucose-lowering agents

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Figure 1 Sites of action of glucose-lowering agents Figure 1 | Sites of action of glucose-lowering agents. Multiple genetic and environmental factors give rise to type 2 diabetes mellitus (T2DM) through insulin resistance with pancreatic β-cell failure. Overweight and obesity contribute to insulin resistance in association with increased inflammatory signals and disturbed lipid homeostasis, often preceding the onset of hyperglycaemia by many years and enhancing cardiovascular risk. When insulin secretion is no longer sufficient to overcome insulin resistance, glucose intolerance progresses to T2DM, usually accompanied by pancreatic α-cell dysfunction that elevates glucagon secretion, reduced prandial secretion or activity of incretin hormones such as glucagon-like peptide 1 (GLP-1), alterations to the gut microbiome and disturbances of neural activities controlling hunger–satiety and the circadian regulation of glucose homeostasis. Insulin, sulfonylureas and meglitinides are associated with risk of hypoglycaemia. DPP-4, dipeptidyl peptidase 4; SGLT2, sodium/glucose cotransporter 2. Tahrani, A. A. et al. (2016) Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus Nat. Rev. Endocrinol. doi:10.1038/nrendo.2016.86