Two groundbreaking drugs for the treatment of obesity are expected to hit the market in the coming years, offering significant advantages over existing medications, including the current weight-loss community superstar, Ozempic.

Orforglipron, the first drug, boasts enhanced usability, cost-effectiveness and simplified production. The second drug, retatrutide, exhibits an unparalleled level of effectiveness, potentially setting a new standard for pharmacological obesity treatment.

Phase II clinical trial results for orforglipron and retatrutide were recently presented at a meeting of the American Diabetes Association and published in the New England Journal of Medicine. These trials provided valuable efficacy and dosage data based on a small group of participants.

Endocrinologist Daniel Drucker from the University of Toronto, who was not involved in the research, hailed both drugs as breakthroughs after examining the findings.

Both drugs mimic gut hormones that regulate food passage and appetite by acting on receptors in the brain. As part of the glucagon-like peptide-1 (GLP-1) receptor agonists class, they were initially developed for diabetes treatment but have proven effective for weight loss as well.

In recent years, two GLP-1 receptor agonists — trizepatide (Mounjaro) and semaglutide (Ozempic and Wegovy) — have entered the market, showcasing substantial weight loss benefits. Trizepatide is approved for diabetes treatment, while semaglutide is available for both diabetes and obesity.

However, Wegovy and Mounjaro require weekly injections and belong to the costly peptide molecule category, making production labor-intensive and expensive. Orforglipron, on the other hand, is a non-peptide compound that can be easily manufactured as a pill, making it more affordable. Internal-medicine physician

Sean Wharton, co-author of the orforglipron study, said it will be a game-changer in an article discussing the results of both trials published in the journal Nature.

While orforglipron offers broader accessibility, retatrutide stands out for its unprecedented weight-loss efficacy. In the trial, participants on the highest dosage experienced an average weight loss of 24.2% over 11 months, surpassing the current approved drugs' typical 15–20% weight loss over a similar timeframe.

All participants on higher doses of retatrutide lost at least 5% of their body weight, compared to the currently approved drugs, which work for around 90% of patients.

Managing obesity specialist Beverly Tchang emphasized in the Nature article that the ability of retatrutide to interact with three receptors associated with appetite likely accounts for its superior effectiveness. In contrast, Wegovy interacts with one receptor, and Mounjaro interacts with two.

While side effects such as nausea and vomiting can occur with Wegovy and Mounjaro, the new drugs may present similar challenges. However, Wharton believes clinicians can effectively mitigate side effects by gradually increasing the dosage.

It is important to note that people taking orforglipron or retatrutide may regain weight upon discontinuation due to the biological factors underlying obesity. The human brain appears to have a set point for body fat storage, and these drugs merely mask it rather than alter it.

While long-acting drugs alone cannot address the root causes of the obesity epidemic, such as limited access to healthy food and exercise, they provide a revolutionary step forward in tackling the crisis. These new medications offer hope for individuals seeking relief from obesity.