GIPR/GLP-1R dual agonist therapies for diabetes and weight loss—chemistry, physiology, and clinical applications

JE Campbell, TD Müller, B Finan, RD DiMarchi… - Cell Metabolism, 2023 - cell.com
The incretin system is an essential metabolic axis that regulates postprandial metabolism.
The two incretin peptides that enable this effect are the glucose-dependent insulinotropic …

Incretin hormones and type 2 diabetes

MA Nauck, TD Müller - Diabetologia, 2023 - Springer
abstract Incretin hormones (glucose-dependent insulinotropic polypeptide [GIP] and
glucagon-like peptide-1 [GLP-1]) play a role in the pathophysiology of type 2 diabetes. Along …

Structural insights into multiplexed pharmacological actions of tirzepatide and peptide 20 at the GIP, GLP-1 or glucagon receptors

F Zhao, Q Zhou, Z Cong, K Hang, X Zou… - Nature …, 2022 - nature.com
Glucose homeostasis, regulated by glucose-dependent insulinotropic polypeptide (GIP),
glucagon-like peptide-1 (GLP-1) and glucagon (GCG) is critical to human health. Several …

Recent advances in incretin-based pharmacotherapies for the treatment of obesity and diabetes

Q Tan, SE Akindehin, CE Orsso, RC Waldner… - Frontiers in …, 2022 - frontiersin.org
The incretin hormone glucagon-like peptide-1 (GLP-1) has received enormous attention
during the past three decades as a therapeutic target for the treatment of obesity and type 2 …

[HTML][HTML] GLP-1 and GIP receptor signaling in beta cells–a review of receptor interactions and co-stimulation

A Mayendraraj, MM Rosenkilde, LS Gasbjerg - Peptides, 2022 - Elsevier
Glucagon-like peptide 1 receptor (GLP-1R) and glucose-dependent insulinotropic
polypeptide receptor (GIPR) are two class B1 G protein-coupled receptors, which are …

Brain uptake pharmacokinetics of albiglutide, dulaglutide, tirzepatide, and DA5-CH in the search for new treatments of Alzheimer's and Parkinson's diseases

EM Rhea, A Babin, P Thomas, M Omer, R Weaver… - Tissue …, 2024 - Taylor & Francis
Background A number of peptide incretin receptor agonists (IRAs) show promise as
therapeutics for Alzheimer's disease (AD) and Parkinson's disease (PD). Transport across …

Tirzepatide: A systematic update

I Forzano, F Varzideh, R Avvisato… - International Journal of …, 2022 - mdpi.com
Tirzepatide is a new molecule capable of controlling glucose blood levels by combining the
dual agonism of Glucose-Dependent Insulinotropic Polypeptide (GIP) and Glucagon-Like …

Designing a dual GLP-1R/GIPR agonist from tirzepatide: comparing residues between tirzepatide, GLP-1, and GIP

L Wang - Drug design, development and therapy, 2023 - Taylor & Francis
Improving type 2 diabetes using incretin analogues is becoming increasingly plausible.
Currently, tirzepatide is the most promising listed incretin analogue. Here, I briefly explain …

Obesity pharmacotherapy: incretin action in the central nervous system

GA Boer, DL Hay, A Tups - Trends in Pharmacological Sciences, 2023 - cell.com
The prevalence of obesity is rising, creating an urgent need for efficacious therapies. Recent
clinical trials show that tirzepatide, a dual agonist of receptors for the incretin hormones …

Engineered mini-G proteins block the internalization of cognate GPCRs and disrupt downstream intracellular signaling

Y Manchanda, L ElEid, AI Oqua, Z Ramchunder… - Science …, 2024 - science.org
Mini-G proteins are engineered, thermostable variants of Gα subunits designed to stabilize
G protein–coupled receptors (GPCRs) in their active conformations. Because of their small …