Pharmacological Advances in Incretin-Based Polyagonism: What We Know and What We Don’t

Feb 14, 2024Physiology (Bethesda, Md.)

New Drug Developments Combining Incretin Hormones: Known Benefits and Unknowns

AI simplified

GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗

Abstract

Obesity is strongly associated with increased incidence of type 2 diabetes, heart failure, certain types of cancer, and all-cause mortality.

Pharmacological attempts to address obesity have historically faced challenges due to limited effectiveness and side effects.
Recent advancements include biochemically optimized drugs targeting the GLP-1 receptor and coagonists for GLP-1 and GIP receptors.
GIP receptor:GLP-1R coagonists may offer improved treatment options for obesity and diabetes compared to GLP-1R monoagonists.
Uncertainties persist regarding the role of GIP in metabolic processes and whether its activation or inhibition is beneficial in conjunction with GLP-1R agonism.
Recent findings highlight the need for further investigation into how the GIP system influences energy and glucose metabolism.

AI simplified

The prevalence of obesity continues to rise in both adolescents and adults, in parallel obesity is strongly associated with the increased incidence of type 2 diabetes, heart failure, certain types of cancer, and all-cause mortality. In relation to obesity, many pharmacological approaches of the past have tried and failed to combat the rising obesity epidemic, particularly due to insufficient efficacy or unacceptable side effects. However, while the history of antiobesity medication is plagued by failures and disappointments, we have witnessed over the last 10 years substantial progress, particularly in regard to biochemically optimized agonists at the receptor for glucagon-like peptide-1 (GLP-1R) and unimolecular coagonists at the receptors for GLP-1 and the glucose-dependent insulinotropic polypeptide (GIP). Although the GIP receptor:GLP-1R coagonists are being heralded as premier pharmacological tools for the treatment of obesity and diabetes, uncertainty remains as to why these drugs testify superiority over best-in-class GLP-1R monoagonists. Particularly with regard to GIP, there remains great uncertainty if and how GIP acts on systems metabolism and if the GIP system should be activated or inhibited to improve metabolic outcome in adjunct to GLP-1R agonism. In this review, we summarize recent advances in GLP-1- and GIP-based pharmacology and discuss recent findings and open questions related to how the GIP system affects systemic energy and glucose metabolism.

Full Text

Full text is available at the source.

View full text ↗

Pharmacological Advances in Incretin-Based Polyagonism: What We Know and What We Don’t

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief