Session 5. Keynote lecture. New horizons in incretin therapies (part 2) Multiple antagonists & agonists

New horizons in incretin therapies (part 2) Multiple antagonists & agonists

  Timo Müller
  Director of the Institute for Diabetes and Obesity at Helmholtz Munich

Timo Müller is the Director of the Institute for Diabetes and Obesity at Helmholtz Munich, and a full Professor for energy and glucose metabolism at the Walther-Straub-Institute for Pharmacology and Toxicology, Ludwig-Maximilians-University Munich (LMU). Dr. Müller is a globally recognized scientist who has achieved considerable international acclaim for his research on incretin-based pharmacology. His notable contributions include the identification of the brain GIP system as a crucial regulator of energy metabolism.

Additionally, he has played a pivotal role in developing innovative pharmacological concepts for treating obesity and diabetes. Continuously at the forefront of diabetes research, Dr. Müller's work has significantly advanced our understanding of how gut hormone therapeutics can effectively address obesity and diabetes. His studies, starting with the demonstration of the superiority of GLP-1-based combination therapies over GLP-1 monotherapies for enhancing glucometabolic control in obese rodents, have been instrumental (Clemmensen et al., Diabetes 2014; Clemmensen et al., EMBO Mol Med 2015).

Dr. Müller is a co-pioneer of the concept of peptidemediated nuclear hormone delivery, presenting it as a novel pharmacological strategy for treating obesity, diabetes, and dyslipidemia (Finan et al., Cell 2016; Sachs et al., Nat Metab 2020; Quarta et al., Nat Metab 2022).


Unimolecular polyagonists targeting the receptors for glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are best-in-class drugs to treat obesity and diabetes. But while GIPR:GLP-1R co-agonists outperform GLP-1 monotherapies to yield greater weight loss and further inhibition of food intake, it remains unclear if and how GIP contributes to enhanced efficacy of these new class of drugs. 

Using a series of conditional KO Models, we recently set out to delineate where and how GIP and its long-acting analogs act in the brain and the periphery to affect systemic energy metabolism. Our data not only identified CNS GIPR signaling as a novel central regulator of systemic energy metabolism in rodents, but also let to the identification of a specific subset of GIPR neurons in the brain as the key neurons underlying body weight reduction and food intake inhibition by GIPR agonism.