Glucagon-like peptide-1 (GLP-1) receptor agonists improve glucose homeostasis, reduce bodyweight, and over time benefit cardiovascular health in type 2 diabetes mellitus (T2DM). However, dose-related gastrointestinal effects limit efficacy, and therefore agents possessing GLP-1 pharmacology that can also target alternative pathways may expand the therapeutic index. One approach is to engineer GLP-1 activity into the sequence of glucose-dependent insulinotropic polypeptide (GIP). Although the therapeutic implications of the lipogenic actions of GIP are debated, its ability to improve lipid and glucose metabolism is especially evident when paired with the anorexigenic mechanism of GLP-1. We review the complexity of GIP in regulating adipose tissue function and energy balance in the context of recent findings in T2DM showing that dual GIP/GLP-1 receptor agonist therapy produces profound weight loss, glycemic control, and lipid lowering.

中文翻译：

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GIP 如何增强 GLP-1 的治疗效果？

胰高血糖素样肽-1 (GLP-1) 受体激动剂可改善葡萄糖稳态，减轻体重，并随着时间的推移有益于 2 型糖尿病 (T2DM) 的心血管健康。然而，剂量相关的胃肠道效应限制了疗效，因此具有 GLP-1 药理学的药物也可以靶向替代途径可能会扩大治疗指数。一种方法是将 GLP-1 活性改造为葡萄糖依赖性促胰岛素多肽 (GIP) 的序列。尽管 GIP 的脂肪生成作用的治疗意义存在争议，但当与 GLP-1 的厌食机制配对时，其改善脂质和葡萄糖代谢的能力尤为明显。