[Glucagon-like peptide-1 receptor agonists: a new pharmacological treatment option for psychiatric illnesses?]

Abstract

Albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, orforglipron and semaglutide are glucagon-like peptide‑1 (GLP-1) receptor agonists. Tirzepatide targets not only GLP‑1 but also glucose-dependent insulinotropic peptide (GIP) receptors and retatrutide is a triple GLP‑1, GIP and glucagon receptor agonist. The GLP‑1 receptor agonists increase insulin release but suppress glucagon release. They slow down the emptying of the stomach and thus prevent blood sugar spikes. They reduce appetite and food intake. In the brain GLP‑1 receptor agonists lead to a better glycemic control and they appear to have anti-inflammatory and neuroprotective effects. It has been reported that GLP‑1 receptor agonists reduce oxidative stress and apoptosis, lower the risk of ischemia and promote neurogenesis. The GLP‑1 receptor agonists can also influence dopaminergic signal transduction in the nucleus accumbens. Therefore, they could modify the effect of cocaine, alcohol and nicotine. Preliminary investigations provide indications of the therapeutic benefits of GLP‑1 receptor agonists for people with dementia, eating disorders, psychopharmacologically induced weight gain, depression, anxiety and substance use disorders. Typical accompanying adverse reactions are gastrointestinal side effects, such as nausea, vomiting, diarrhea, eructation and gastroesophageal reflux. More severe side effects include pancreatitis, allergic reactions, renal function disorders and possibly an increased risk of thyroid cancer.