Are peptide conjugates the golden therapy against obesity?

• Published in: Journal of endocrinology Vol. 238; no. 2; pp. R109 - R119
• Main Authors: Brandt, S J, Kleinert, M, Tschöp, M H, Müller, T D
• Format: Journal Article
• Language: English
• Published: England Bioscientifica Ltd 01.08.2018; Portland Press Ltd The Biochemical Society
• Subjects: Animals; Anti-Obesity Agents - chemical synthesis; Anti-Obesity Agents - classification; Anti-Obesity Agents - therapeutic use; Bariatric Surgery; Body weight loss; Clinical trials; Diabetes mellitus; Drug Discovery; Drug metabolism; Drugs; Energy Metabolism - drug effects; Exercise Therapy; Gastrointestinal surgery; GIP protein; Glucagon; Glucagon-like peptide 1; Humans; Life Style; Obesity; Obesity - drug therapy; Obesity - metabolism; Obesity - therapy; Pandemics; Peptides - chemistry; Peptides - therapeutic use; Remission; Review; Surgery; Weight control; Weight Reduction Programs - methods; peptides; metabolism; diabetes; obesity
• ISSN: 0022-0795; 1479-6805
• DOI: 10.1530/JOE-18-0264

Obesity is a worldwide pandemic, which can be fatal for the most extremely affected individuals. Lifestyle interventions such as diet and exercise are largely ineffective and current anti-obesity medications offer little in the way of significant or sustained weight loss. Bariatric surgery is effective, but largely restricted to only a small subset of extremely obese patients. While the hormonal factors mediating sustained weight loss and remission of diabetes by bariatric surgery remain elusive, a new class of polypharmacological drugs shows potential to shrink the gap in efficacy between a surgery and pharmacology. In essence, this new class of drugs combines the beneficial effects of several independent hormones into a single entity, thereby combining their metabolic efficacy to improve systems metabolism. Such unimolecular drugs include single molecules with agonism at the receptors for glucagon, glucagon-like peptide 1 and the glucose-dependent insulinotropic polypeptide. In preclinical studies, these specially tailored multiagonists outperform both their mono-agonist components and current best in class anti-obesity medications. While clinical trials and vigorous safety analyses are ongoing, these drugs are poised to have a transformative effect in anti-obesity therapy and might hopefully lead the way to a new era in weight-loss pharmacology.