Session 5. Keynote lecture. Dual agonists, new horizons in incretin therapies

Dual agonists, new horizons in incretin therapies

  Michael Nauck
  Head of Clinical Research at the Diabetes Division of St. Josef-Hospital (Ruhr-University Bochum)

Professor Nauck has a particular research interest in the role of gastrointestinal peptide hormones (incretins: glucose-dependent insulinotropic polypeptide, GIP, and glucagon-like peptide-1, GLP-1) in the physiological regulation of metabolism and in the pathophysiology of type 2 diabetes. He has contributed pivotal studies proving a therapeutic potential of GLP-1 in type 2 diabetes. He has contributed to the development of incretin-based glucose-lowering medications such as GLP-1 receptor agonists and inhibitors of dipeptidyl peptidase-4. Additional areas of interest include spontaneous hypoglycaemia (insulinomas), pancreas transplantation, cardiovascular complications of type 2 diabetes, and the modification of cardiovascular risk in type 2-diabetic patients with glucose-lowering pharmacotherapy. His scientific contributions have been honoured with several awards, including the Ferdinand-Bertram Award (1993), the Werner-Creutzfeldt Award (2007) and the Paul Langerhans Medal (2012) from the German Diabetes Association, and the Claude Bernard Medal from the European Association for the Study of Diabetes (2022).

He has served as reviewer for all major diabetes journals and has published more than 245 original articles and 130 reviews and book chapters. His publications have been quoted > 84000 times, his “H-index” is 108, and he has been a “highly-cited researcher” (among the top 1 %) in 2019 (Web of Knowledge). Professor Nauck is member of a number of professional societies, including the German, European, American Diabetes Associations, and the International Diabetes Federation.

Obesity and diabetes reached a high prevalence. In recent years, progress has been made through the discovery of a new class of medicines: the gut-hormone co-agonists. These novel therapeutics combine action on GLP-1 plus other gut hormone receptors within a single molecule, thereby augmenting metabolic benefits. The first of these engineered unimolecular compounds exerted balanced co-agonism at glucagon like-1 (GLP-1) and glucagon receptors, reported in 2009. Other co-agonists under development include dual GLP-1/gastric inhibitory peptide (GIP) co-agonists, first described in 2013, and triple GLP-1/ GIP/glucagon co-agonists, initially designed in 2015. In 2022, a GIP/GLP-1 co-agonist named Tirzepatide has been approved for the treatment of type 2 diabetes, providing superior HbA1c target achievement compared to basal insulin or selective GLP-1 RA treatment and unprecedented average weight loss (up to 22.5% in non-diabetic, obese subjects). It is the purpose of this talk to summarize the discovery, development, and mechanism of action of these gut hormone co-agonists, and to discuss potential challenges, limitations and future developments.

Learning outcomes;

1. Understanding the difference between various co-agonists depending on the receptors addressed by a given molecule

2. Demonstrating the augmented effectiveness on glycaemic control and body weight versus selective GLP-1 receptor agonists


1. To provide information on the rationale for the development of multihormone co-agonists

2. To show the similarity in mechanisms of action of co-agonists with multiple gut hormones determining diabetes control and weight loss after bariatric surgery