Experimental weight-loss drugs could challenge Mounjaro’s dominance

Wednesday 02 September 2026 - 12:42

By: Azzat Manal

Experimental weight-loss drugs could challenge Mounjaro’s dominance

New experimental weight-loss medicines could soon challenge the leading position of Mounjaro after clinical trials showed that some next-generation treatments may help patients lose around a quarter of their body weight in less than a year.

Among the most promising candidates is retatrutide, which has earned the nickname “Godzilla” because of the scale of weight loss reported in trials. Participants receiving the drug lost nearly 25% of their body weight over 48 weeks. Another experimental treatment, amycretin, produced similarly encouraging results over a shorter period of 36 weeks.

Neither drug has yet received approval for widespread use, meaning their effectiveness and safety are still being assessed through clinical research.

Mounjaro, whose active ingredient is tirzepatide, currently ranks among the most effective widely available injectable treatments for weight management. Clinical data have shown average weight reductions of more than 20% after roughly 17 months of treatment. Semaglutide-based medicines, including Wegovy and Ozempic, have also demonstrated significant weight-loss effects, with reductions reaching about 18.7% over a comparable period.

Researchers from McGill University and the Jewish General Hospital in Montreal reviewed 38 clinical trials involving more than 25,000 participants to compare the effectiveness and safety of different weight-loss medications.

One possible explanation for the differences in results is the way these treatments interact with hormones involved in appetite, blood sugar regulation and energy balance. Semaglutide primarily mimics the GLP-1 hormone, which promotes feelings of fullness and helps reduce appetite. Tirzepatide acts on both GLP-1 and GIP, two hormonal pathways involved in appetite and glucose regulation.

Retatrutide goes further by targeting three hormonal pathways: GLP-1, GIP and glucagon. The latter is involved in regulating blood sugar and may also increase the body's energy expenditure. Amycretin combines GLP-1 activity with the effects of amylin, a pancreatic hormone that contributes to satiety, slows stomach emptying and helps regulate blood glucose.

Scientists believe that targeting several hormonal pathways simultaneously could potentially produce greater weight loss than treatments acting on a single pathway. However, the long-term benefits and risks of these newer medicines remain under investigation.

Side effects remain another important consideration. Gastrointestinal problems such as nausea, vomiting, diarrhea and constipation were among the most frequently reported reactions. Across the studies reviewed, about 76% of participants receiving weight-loss medicines experienced gastrointestinal side effects, compared with around 40% in placebo groups. Approximately 10% of participants discontinued treatment because of adverse effects.

The review also identified rare cases involving bile duct disorders, pancreatitis and psychiatric complications, as well as six reported deaths. The researchers stressed that the clinical trials differed in their design and methodology, meaning the results should not be interpreted as a direct head-to-head comparison between every medication.

The findings, published in the journal Annals of Internal Medicine, nevertheless point to a rapidly evolving field. As pharmaceutical companies develop medicines capable of targeting multiple biological pathways, the next generation of obesity treatments could significantly reshape the market — provided their safety and effectiveness are confirmed in larger and longer-term studies.