Clinical innovation and scientific progress in GLP-1 medicine
Series edited by Daniel J. Drucker
Therapies targeting the glucagon-like peptide 1 (GLP-1) receptor have revolutionized the treatment of obesity and diabetes. This series of reviews, curated by Dr. Dan Drucker, describes the latest research in this fast-moving in field, from our evolving understanding of the mechanism of GLP-1 receptor signaling to the medicines’ impact on inflammation and the consequences for heart, kidney, and brain health. The reviews also explore the impact of these medicines on conditions beyond their initial indications, including cancer and neurodegenerative disease risk.
Articles in series
Abstract
Cancer diagnoses are prevalent in people with obesity and type 2 diabetes, and abundant clinical evidence supports the protective effects of weight loss for cancer prevention. Glucagon-like peptide-1 (GLP-1) receptor agonists have revolutionized obesity and type 2 diabetes medicine and alleviate many comorbidities of these metabolic diseases. In this Review, we summarize the current clinical evidence for GLP-1 receptor agonists and cancer risk, including thyroid, pancreatic, gastrointestinal, and hormone-dependent malignancies. With few exceptions, recent meta-analyses report that GLP-1 receptor therapies do not increase cancer incidence and may lower risk in some cases. Preclinical studies reinforce the anticancer effects of GLP-1 receptor therapies, even in non-obese models. However, there are still many opportunities for translational insight as the field grows. Immune-modulating effects of GLP-1 receptor agonists are reported in several preclinical cancer studies, which may reflect direct action on immune cells or result from improved metabolic function. We highlight ongoing clinical trials for GLP-1 receptor therapies in cancer patients, and offer considerations for preclinical studies, including perspectives on the timing and duration of GLP-1 receptor agonist treatment, concurrent use of standard anticancer therapies, and interpretation of models of cancer risk versus progression.
Authors
Estefania Valencia-Rincón, Rajani Rai, Vishal Chandra, Elizabeth A. Wellberg
Abstract
Glucagon-like peptide-1 (GLP-1) was initially considered to be a hormone with a predominant role in regulating glucose metabolism by inducing insulin secretion, reducing glucagon secretion, and ameliorating insulin resistance, with the last effect being largely dependent on the induction of weight loss. In more recent years, the role of this peptide beyond metabolism has progressively been explored, including its impact on kidney physiology and kidney clinical outcomes in people with obesity with or without diabetes. Indeed, despite only modest expression of the GLP-1 receptor in the kidney, the renoprotective actions of GLP-1 and its receptor agonists have become an area of intensive investigation. This Review appraises the current status of GLP-1 peptide and its receptor agonists and focuses on the preclinical as well as recent seminal clinical findings defining the kidney benefits conferred by GLP-1 receptor agonist treatment in people living with type 2 diabetes and obesity.
Authors
Mark E. Cooper, Daniël H. van Raalte
Abstract
Therapies based on glucagon-like peptide-1 (GLP-1) reduce rates of cardiovascular and chronic kidney disease in people with type 2 diabetes and/or obesity, with ongoing clinical trials investigating their effects in people with metabolic liver disease, arthritis, and both substance use and neurodegenerative disorders. Acute and chronic activation of GLP-1 receptor signaling also reduces systemic and tissue inflammation in mice and humans, through weight loss–dependent and –independent mechanisms, actions that may contribute to the expanding spectrum of clinical benefits ascribed to GLP-1 medicines. In this Review, we highlight current understanding of the direct and indirect antiinflammatory effects and mechanisms of GLP-1 medicines in both preclinical and clinical studies, covering emerging concepts, clinical relevance, and areas of uncertainty that require further investigation.
Authors
Chi Kin Wong, Daniel J. Drucker
Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)