The Impact of Incretin-Based Medications on Lipid Metabolism

Abstract

Pathophysiological pathways that are induced by chronic hyperglycemia negatively impact lipid metabolism. Thus, diabetes is commonly accompanied by varying degrees of dyslipidemia which is itself a major risk factor for further macro- and microvascular diabetes complications such as atherosclerosis and nephropathy. Therefore, normalizing lipid metabolism is an attractive goal for therapy in patients with diabetes. Incretin-based medications are a novel group of antidiabetic agents with potent hypoglycemic effects. While the impact of incretins on glucose metabolism is clear, recent evidence indicates their positive modulatory roles on various aspects of lipid metabolism. Therefore, incretins may offer additional beneficial effects beyond that of glucose normalization. In the current review, how these antidiabetic medications can regulate lipid homeostasis and the possible cellular pathways involved are discussed, incorporating related clinical evidence about incretin effects on lipid homeostasis.

The effect of glucagon‐like peptide‐1 receptor agonists on serum uric acid concentration: A systematic review and meta‐analysis

“…[2][3][4][5][6][7][8] Since their introduction, several different formulations of these antidiabetic agents have been brought to market; to date, seven injectable analogues (twicedaily exenatide immediate-release, once-weekly exenatide extendedrelease, once-daily liraglutide, once-daily lixisenatide, once-weekly albiglutide [currently off-market due to a decline in sales], onceweekly dulaglutide and once-weekly semaglutide) and one orallyadministered analogue (once-daily semaglutide) have been approved by the Food and Drug Administration (FDA). 9 Besides GLP-1 receptor as their putative target, numerous molecular targets have been identified for GLP-1 RAs, [10][11][12][13][14][15][16][17][18][19] which justifies their potential for wider medical applications. In this context, several studies have demonstrated that GLP-1 RAs can alter serum uric acid (SUA) concentration.…”

Lipid regulation of the glucagon receptor family

“…Current literature highlights the importance of lipids on the function of GPCRs, with cholesterol playing a direct role as a potential allosteric modulator as well as an indirect effect related to the segregation of these receptors to cholesterol-rich nanodomains in the plasma membrane. While most of the work done regarding lipids and the glucagon receptor family has revolved around incretin receptor regulation of lipid metabolism ( Yaribeygi et al . 2021 ), there is currently sparse information about the regulation of GLP-1R and GLP-2R by lipids, and little to no information about the regulation of GIPR, either directly or indirectly due to lipid modification of GIPR agonists.…”

Anti-inflammatory benefits of semaglutide: State of the art

“…Incretins are hormones released by the enteroendocrine L-cells of the gastrointestinal (GI) tract in response to food intake [38] . They stimulate the release of insulin from the pancreas and reduce the production of glucagon, helping to normalize postprandial glucose levels [38] , [39] . Incretin-based medications mimic the actions of natural incretins, such as GLP-1 and gastric inhibitory hormone (GIP).…”