Polyagonists - the future of obesity treatment
The projected golden era of obesity treatment using the various polyagonist drugs in development is the subject of a presentation at this year’s International Congress on Obesity in Sao Paulo, Brazil (26-29 June) by Prof Carel le Roux, University College Dublin, Ireland.
“We have already entered an incredibly exciting turning point in the treatment of obesity, with semaglutide and tirzepatide being used to treat obesity in many markets,” explains Prof le Roux. “The development pipeline for new anti-obesity medications is incredibly active, with many companies entering the race and already several promising drugs in various stages of clinical trials and research.”
“There is also great excitement regarding Retatrutide, which is currently in phase 3 clinical trials. Retatrutide is a triple agonist that stimulates glucagon-like peptide-1 receptor (GLP-1), Glucose-dependent insulinotropic polypeptide (GIP), and glucagon receptors (GCGR). With projected 25% weight loss after 1 year, improvements in liver disease, and diabetes this medication is mimicking the benefits of bariatric surgery.”
Prof le Roux will also discuss other drugs showing great promise include survodutide, also in phase 3 clinical trials, shows significant promise in treating obesity, especially in those patients with metabolic dysfunction-associated steatohepatitis (MASH). “This is a dual agonist targeting both the GCGR and GLP-1R,” says Prof le Roux. “This dual mechanism inhibit appetite and may enhance energy expenditure. The weight loss independent benefits including reversing liver fibrosis also holds significant promise.”
Elsewhere, Cagrisema, a combination of semaglutide and the amylin anologue, cagrilintide, is in phase 3 clinical trials showing promise for treating obesity. Phase 2 clinical trials have demonstrated that Cagrisema can lead to substantial weight loss and improved blood sugar control in individuals with type 2 diabetes and obesity and may be first drug to have similar weight loss in patients with and without type 2 diabetes. For other obesity drugs results tend to be better for patients without type 2 diabetes.
As well as these examples, Prof le Roux will discuss several new polyagonists that are also entering phase 1 and phase 2 trials and showing tremendous potential.
Regarding side effects and safety, he explains that “the safety profile of the new polyagonists are all favourable, with common side effects being gastrointestinal in nature, such as nausea and vomiting, which are consistent with other GLP-1 medications used since 2005. Attenuation of the rapid dose titration schemes may help reduce the short-term side effects.”
He will also sound a note of caution that the current euphoria regarding potential average weight loss of 25% for some of these new drug class medications may have reduced the focus on how we can optimise their use in the long term. “A renewed focus should be on reducing potential side effects associated with effectively controlling obesity by using medications that address subcortical areas of the brain in a similar way as we have done for bariatric surgery over the last 50 years. We have learnt the hard way regarding the long-term side effects with bariatric surgery and we do not need to reinvent the wheel. We will have retatrutide, survodutide, and CagriSema available almost simultaneously and we will be able to optimise the benefits while reducing short- and long-term side effects.”
Prof Carel le Roux, University College Dublin, Ireland. Please contact via e-mail E) carel.leroux@ucd.ie
ICO 2024
The International Congress on Obesity (ICO 2024) is hosted by the World Obesity Federation, in partnership with member organisation the Associação Brasileira para o Estudo da Obesidade (ABESO). ICO 2024 takes place at the Frei Caneca Conventions Center in São Paulo from 26 - 29 June.
ICO 2024