GIP Is 1 of 2 Incretin Hormones—Along With GLP-1—That Has Diverse Metabolic Roles1
Glucose dependent Insulinotropic Polypeptide (GIP) and Glucagon-Like Peptide-1 (GLP-1) drive the incretin effect, which leads to insulin release and postprandial glucose clearance1
These hormones are secreted by the gut in response to nutrient load. They are responsible for the incretin effect, which enhances the secretion of insulin after a meal.2
GIP is responsible for nearly two-thirds of the incretin effect in healthy humans, contributing more to insulin secretion than GLP-1.1
The incretin effect is diminished in patients with Type 2 Diabetes (T2D)1
A diminished incretin effect is associated with hyperglycemia. Over time, hyperglycemia is associated with nephropathy, retinopathy, neuropathy, and cardiovascular disease.1,3
Recent studies suggest several additional functions for GIP and GLP-14-7
GLP-1 is known to regulate body weight via its actions in the CNS. Similarly, GIP receptors are found in areas of the CNS that may regulate body weight through appetite and food intake mechanisms.8-10
Preclinical studies have also shown GIP receptors in areas of the brain known to act on appetite control centers, which may reduce caloric consumption.8,11,12
While GLP-1 RAs can improve insulin sensitivity in patients with T2D, it may be the result of weight loss. But GIP has displayed direct effects on insulin sensitivity in preclinical studies.4-5
Comparison of Proposed Actions of GIP And GLP-15

Derived from preclinical studies: Samms RJ, Coghlan MP, Sloop KW. How may GIP enhance the therapeutic efficacy of GLP-1? Trends Endocrinol Metab. 2020;31(6):416.4
Schematic depiction of proposed pleiotropic actions of GIP and GLP-1
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LEARN MORECNS=central nervous system; GIP=glucose-dependent insulinotropic polypeptide; GLP-1=glucagon-like peptide-1; RA=receptor agonist; GLP-1 RA=glucagon-like peptide-1 receptor agonist; T2D=type 2 diabetes.
References:
- Nauck MA, Meier JJ. GIP and GLP-1: stepsiblings rather than monozygotic twins within the incretin family. Diabetes. 2019;68(5):897-900.
- Nauck MA, Meier JJ. The incretin effect in healthy individuals and those with type 2 diabetes: physiology, pathophysiology, and response to therapeutic interventions. Lancet Diabetes Endocrinol. 2016;4(6):525-536.
- American Diabetes Association. Standards of medical care in diabetes—2022. Diabetes Care. 2022;45(suppl1):S1-S264.
- Mohammad S, Ramos LS, Buck J, et al. Gastric inhibitory peptide controls adipose insulin sensitivity via activation of cAMP-response element-binding protein and p110β isoform of phosphatidylinositol 3-kinase. J Biol Chem. 2011;286(50):43062-43070.
- Samms RJ, Coghlan MP, Sloop KW. How may GIP enhance the therapeutic efficacy of GLP-1? Trends Endocrinol Metab. 2020;31(6):410-421.
- Finan B, Müller TD, Clemmensen C, et al. Reappraisal of GIP pharmacology for metabolic diseases. Trends Mol Med. 2016;22(5):359-376.
- Nauck MA, Quast DR, Wefers J, Pfeiffer AFH. The evolving story of incretins (GIP and GLP- 1) in metabolic and cardiovascular disease: A pathophysiological update. Diabetes Obes Metab. 2021;23(suppl 3):5-29.
- Adriaenssens AE, Biggs EK, Darwish T, et al. Glucose-dependent insulinotropic polypeptide receptor-expressing cells in the hypothalamus regulate food intake. Cell Metab. 2019;30(5):987-996.e6.
- Samms RJ, Coghlan MP, Sloop KW. How may GIP enhance the therapeutic efficacy of GLP-1? Trends Endocrinol Metab. 2020;31(6):410-421.
- van Bloemendaal L, ten Kulve JS, la Fleur SE, et al. Effects of glucagon-like peptide 1 on appetite and body weight: focus on the CNS. J Endocrinol. 2014;221(1):T1-T16.
- Adriaenssens AE, Gribble FM, Reimann F. The glucose-dependent insulinotropic polypeptide signaling axis in the central nervous system. Peptides. 2020;125(3):170194
- Samms RJ, Sloop KW, Gribble FM, et al. GIPR function in the central nervous System: implications and novel perspectives for GIP-based therapies in treating metabolic disorders. Diabetes. 2021;70(9):1938-1944.