How May GIP Enhance the Therapeutic Efficacy of GLP-1?

被引:262
作者
Samms, Ricardo J. [1 ]
Goghlan, Matthew P. [1 ]
Sloop, Kyle W. [1 ]
机构
[1] Eli Lilly & Co, Lilly Res Labs, Diabet & Complicat, Indianapolis, IN 46285 USA
关键词
GASTRIC-INHIBITORY POLYPEPTIDE; DEPENDENT INSULINOTROPIC POLYPEPTIDE; GLUCAGON-LIKE PEPTIDE-1; LIPOPROTEIN-LIPASE ACTIVITY; ADIPOSE-TISSUE METABOLISM; FUNCTIONAL EXPRESSION; RECEPTOR AGONIST; WEIGHT-LOSS; BLOOD-FLOW; 7-36; AMIDE;
D O I
10.1016/j.tem.2020.02.006
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Glucagon-like peptide-1 (GLP-1) receptor agonists improve glucose homeostasis, reduce body weight, 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.
引用
收藏
页码:410 / 421
页数:12
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