Polyagonists Enable Increasingly Effective Treatment of Obesity and Diabetes

Dual and Triple Incretin‑Based Co‑agonists: Novel Therapeutics for Obesity and Diabetes. Diabetes Therapy 2024


The drug semaglutide, a GLP-1 receptor agonist, was developed for the treatment of type 2 diabetes (T2D). However, it is also currently widely discussed as a “slimming injection”. Polyagonists that combine several hormones achieve even more impressive results in the treatment of obesity and T2D. With dual and triple agonists, clinical studies are now achieving results that are otherwise only known from bariatric surgery. In the “Diabetes Therapy” journal, researchers from the DZD and Helmholtz Munich provide an overview of these new diabetes and obesity drugs.

More and more people around the world are suffering from obesity and/or type 2 diabetes. New effective treatment options are urgently needed. The discovery of long-acting incretin receptor agonists was a major step forward.

Incretins are hormones produced in the intestine that regulate the release of the blood sugar-lowering hormone insulin during food intake. By inhibiting the insulin antagonist glucagon, they also stimulate the satiety center in the brain. Synthetic incretin receptor agonists are similar to natural incretins and can mimic their effect.

Researchers from the German Center for Diabetes Research (DZD) and Helmholtz Munich, in collaboration with a colleague from the University of Santiago de Compostela in Spain, describe the development of incretin-based pharmacotherapy from its beginnings to the discovery of polyagonists. According to the group of authors, these polyagonists are “in all likelihood the next step towards a cure for diabetes and obesity.”

Comparable to bariatric surgery
The authors report on various polyagonists that are currently being researched in clinical studies and “show improved efficacy with each new generation.” The latest triple agonists attack both the glucose-dependent insulinotropic peptide receptor (GIPR) and the receptors for glucagon-like peptide 1 (GLP1) and glucagon (GCG, a hormone from the pancreas). According to the study reports, their effect can rival that of bariatric surgery – both in terms of treating diabetes and obesity.

Nevertheless, the authors warn against too much euphoria, as there are still some challenges ahead. For example, it is not yet fully understood how incretin receptor agonists achieve their effect on body weight. The safety profile of the new drugs also still needs to be improved, as does patient access to the new therapies.

Original publication:
Robert M. Gutgesell, Rubén Nogueiras, Matthias H. Tschöp, Timo D. Müller. Dual and Triple Incretin‑Based Co‑agonists: Novel Therapeutics for Obesity and Diabetes. Diabetes Therapy 2024 Apr 4; doi: 10.1007/s13300-024-01566-x