Transforming obesity: The advancement of multi-receptor drugs.

For more than a century, physicians have searched for ways to pharmacologically reduce excess body fat. The tide has finally turned with recent advances in biochemically engineered agonists for the receptor of glucagon-like peptide-1 (GLP-1) and their use in GLP-1-based polyagonists. These polyagonists reduce body weight through complementary pharmacology by incorporating the receptors for glucagon and/or the glucose-dependent insulinotropic polypeptide (GIP). In their most advanced forms, gut-hormone polyagonists achieve an unprecedented weight reduction of up to ∼20%-30%, offering a pharmacological alternative to bariatric surgery. Along with favorable effects on glycemia, fatty liver, and kidney disease, they also offer beneficial effects on the cardiovascular system and adipose tissue. These new interventions, therefore, hold great promise for the future of anti-obesity medications.
Competing Interests: Declaration of interests C.M.K. and P.E.S. have sponsored research agreements with Eli Lilly. M.H.T. was a member of the Research Cluster Advisory Panel (ReCAP) of the Novo Nordisk Foundation between 2017 and 2019. He received funding for his research projects by Novo Nordisk (2016–2020) and Sanofi-Aventis (2012–2019). He consulted twice for Boehringer Ingelheim Pharma GmbH & Co. KG (2020 and 2021) and delivered a scientific lecture for Sanofi-Aventis Deutschland GmbH (2020). As CEO and CSO of Helmholtz Munich, he is co-responsible for numerous collaborations of the employees with a multitude of companies and institutions worldwide. In this capacity, he discusses potential projects with and has signed/signs contracts for the Helmholtz institute(s) related to research collaborations worldwide, including but not limited to pharmaceutical corporations like Boehringer Ingelheim, Novo Nordisk, Roche Diagnostics, Arbormed, Eli Lilly, SCG Cell Therapy, and others. As the CEO and CSO of Helmholtz Munich, he was/is further overall responsible for commercial technology transfer activities. M.H.T. confirms that, to the best of his knowledge, none of the above funding sources or collaborations were involved in or had an influence on the preparation of this manuscript. M.H.T. is a former member of the scientific advisory board of ERX, which is developing celastrol, but has no current competing interests. R.D.D. is the co-inventor of multiple patents pertaining to this field that are owned by Indiana University. He was co-founder of Marcadia Biotech and a former employee at Eli Lilly Research labs and Novo Nordisk, advancing drug candidates associated with the subject of this review. T.D.M. receives research funding from Novo Nordisk; however, these funds are unrelated to the work described here. T.D.M. further received speaking fees within the past 3 years from Novo Nordisk, Eli Lilly, AstraZeneca, Merck, Berlin Chemie AG, and Mercodia.
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