GLP1 poly-agonist peptides/ja

GLP1ポリ拮抗ペプチドは、グルカゴン様ペプチド-1（GLP-1）受容体を含む複数のペプチドホルモン受容体を活性化する薬物の一種である。これらの薬物はGLP-1受容体作動薬と同じ適応症、特に肥満症、2型糖尿病、非アルコール性脂肪性肝疾患を対象に開発されている。これらの薬剤は、胃腸障害によって用量が制限されるGLP-1モノ拮抗薬と比較して、より少ない副作用で優れた効果をもたらすことが期待されている。多受容体作動薬の有効性は、おそらく肥満手術と同等かそれを上回る可能性がある。このような薬物で最初に承認を受けたのは、GLP-1とGIP受容体のデュアルアゴニストであるチルゼパチドである。

GLP-1 and GIP receptor dual agonists

Tirzepatide, a dual agonist of GLP-1 and GIP receptors, is approved for type 2 diabetes and obesity. With an average 20 percent weight loss at a high dosage, it appears to be more effective than GLP-1 mono agonists although there have been no head to head trials as of 2023.

GLP-1 and glucagon receptor dual agonists

See also: Glucagon receptor agonist

Glucagon is a hormone that generally opposes the action of insulin. It increases blood glucose by stimulating the production of glucose in the liver via glycogenolysis (breakdown of glycogen) and gluconeogenesis (production of glucose from non-carbohydrate sources). Glucagon also increases the breakdown of lipids and amino acids and the production of ketones. Unlike currently approved weight loss drugs, glucagon receptor agonists increase energy expenditure. Combination GLP-1/glucagon receptor agonists provide the thermogenic benefits of glucagon activation while almost eliminating hyperglycemia induced by glucagon receptor activation. Several such drugs have reached human trials for obesity, diabetes, and non-alcoholic fatty liver disease but adverse effects have hampered development. The most advanced of these drugs is mazdutide which is in a phase III trial as of 2023.

GLP-1, GIP, and glucagon receptor triple agonists

Following the discovery of GLP-1/GIP and GLP-1/glucagon dual agonists, it was hoped that a triple agonist would provide additive or synergistic metabolic benefits. A clinical trial of the triple agonist retatrutide found an average −24.2 percent weight reduction in the highest dosage group after 24 weeks.

Conjugates

Attaching other hormones such as estrogen, thyroid hormone (T3), and dexamethasone to GLP-1 or glucagon restrict the activity of the attached hormone to cells that express GLP-1 or glucagon.

GLP-1 and amylin receptor agonist conjugates have also been tested in preclinical trials.

GLP-1 and neuropeptide Y multi-agonists

In 2023, researchers disclosed the discovery of multiple peptides that activated the GLP-1 receptor, neuropeptide Y receptor Y1, and neuropeptide Y receptor Y2. Since neuropeptide Y receptors were a previous anti-obesity target, it is hoped that the combination might be more efficacious than GLP-1 receptor agonists.

See also

• Cagrilintide/semaglutide
• Insulin icodec/semaglutide