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

Trends Endocrinol Metab. 2020 Jun;31(6):410-421. doi: 10.1016/j.tem.2020.02.006. Epub 2020 Mar 16.


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.

Keywords: LY3298176; NNC00902746; glucagon-like peptide-1; glucose-dependent insulinotropic polypeptide; tirzepatide; type 2 diabetes mellitus.

Publication types

  • Review

MeSH terms

  • Adipose Tissue, White / drug effects*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Gastric Inhibitory Polypeptide / pharmacology*
  • Glucagon-Like Peptide 1 / pharmacology*
  • Glucagon-Like Peptide-1 Receptor / agonists*
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Receptors, Gastrointestinal Hormone / agonists*


  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Receptors, Gastrointestinal Hormone
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1
  • gastric inhibitory polypeptide receptor