A new experimental weight-loss drug, retatrutide, has demonstrated greater efficacy than the current leading medication, tirzepatide, according to a significant review of available treatments. Retatrutide, nicknamed 'Godzilla' due to its potential power, could lead to patients losing nearly a quarter of their body weight after 48 weeks, while tirzepatide, the active ingredient in Mounjaro, resulted in over a fifth of body weight loss in patients over approximately 17 months.
Retatrutide, also known as 'Reta,' has not yet received broad approval for public use. However, it was recently cleared in the United States for a select group of patients with critical needs. Another experimental injection, amycretin, yielded similar weight loss results to retatrutide after just 36 weeks, suggesting these could become the most potent weight-loss treatments developed if approved by health authorities.
For comparison, semaglutide injections, including Wegovy and Ozempic, have shown weight loss of up to 18.7 percent over a comparable period. Mounjaro also appears to achieve greater weight loss than newer once-daily oral treatments like the Wegovy pill and Foundayo, which were recently approved in the UK. The Wegovy pill has been associated with up to 15.5 percent body weight loss over 68 weeks, while Foundayo, also known as orforglipron, has shown up to 14.7 percent weight loss in just 36 weeks.
These findings emerged from a systematic review of 38 trials involving over 25,000 participants, conducted by researchers from McGill University and the Jewish General Hospital in Montreal, Canada. The review examined the safety and effectiveness of various weight-loss drugs, including GLP-1 receptor agonists and newer experimental compounds, against placebos.
Scientists attribute the increasing potency of these drugs to their ability to mimic multiple hormones involved in appetite regulation and metabolism. Semaglutide mimics the gut hormone GLP-1, which increases satiety and reduces appetite. Tirzepatide targets both GLP-1 and GIP (glucose-dependent insulinotropic polypeptide), another hormone involved in appetite and blood sugar control, which experts believe contributes to its superior effectiveness over semaglutide.
Retatrutide, classified as a 'triple agonist,' targets GLP-1, GIP, and glucagon. Glucagon is believed to increase the body's energy expenditure, potentially explaining retatrutide's greater weight loss effects observed in trials. Amycretin targets GLP-1 and amylin, a hormone released after eating that signals fullness to the brain.
The review also analyzed reported side effects. Approximately 76 percent of participants taking the weight-loss injections or pills experienced gastrointestinal side effects, such as diarrhea, vomiting, nausea, and constipation, compared to about 40 percent in the placebo group. Around 10 percent of participants discontinued the medications due to these side effects.
Rare instances of severe biliary disorders, including gallstones, pancreatitis, psychiatric disorders, and six deaths were also noted. The researchers cautioned that differences in trial designs mean direct comparisons between drugs may not be fully conclusive. Separate safety data in the UK has linked hundreds of adverse reactions and a number of deaths to these types of medications, though officials emphasize that such reports do not definitively prove causation.