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The most potent of the drugs currently approved for inducing weight loss has an even stronger effect when combined with another hormone-targeting treatment. The findings suggest that combining the two could lead to more potent weight-loss therapies, an approach that could become available for wider use in the next few years.
“It’s a pretty astonishing degree of weight loss,” says David Preiss at the University of Oxford, who wasn’t involved in the latest research.
Tirzepatide, sold under the brand names Mounjaro and Zepbound, is the most potent approved weight-loss drug. Throughout the world, it is used to treat adults who have type 2 diabetes or obesity, or who are overweight and have at least one weight-related condition, such as high blood pressure. The drug is administered through weekly injections and mimics two appetite-suppressing hormones: GLP-1 and GIP.
Searching for an even stronger alternative, Dan Skovronsky at Eli Lilly in Indiana and his colleagues recruited 367 people from the US and Argentina who were overweight or who had obesity, all of whom had type 2 diabetes.
They randomly split the participants into groups, then gave some a high, 15-milligram dose of tirzepatide each week. Other groups received varying doses of tirzepatide in combination with eloralintide, a drug that targets a different appetite-suppressing hormone, amylin, and was delivered via a second weekly injection. The team named this dual approach EloraTZP. The remaining participants received placebo injections.
Eleven months later, participants receiving only the 15-milligram tirzepatide dose had lost 15.6 kilograms, or about 14.8 per cent of their body weight, on average. In contrast, those who received the highest dose of eloralintide and the 15-milligram dose of tirzepatide lost about 24.5 kilograms on average, equivalent to 23.3 per cent of their body weight. The placebo group lost just 3 per cent of their body weight, on average.
The findings were presented at the 62nd Annual Meeting of the European Association for the Study of Diabetes in Milan, Italy, on 30 September.
“Adding a drug acting like amylin [alongside tirzepatide] effectively brings a third appetite-regulating pathway into play, which may explain why the combination appears to deliver substantially greater weight loss,” says Lora Heisler at the University of Aberdeen, UK, who also wasn’t involved in the work.
The tirzepatide group also experienced a 2.4 per cent reduction, on average, in their blood sugar levels. The same figure was 2.9 per cent in the high-dose EloraTZP group and 0.3 per cent among those on the placebo. “These are massive reductions [with EloraTZP],” says Preiss. “You would imagine that this [and the weight loss] would reduce the risk of cardiovascular complications, high blood pressure,” he says, although further studies exploring this are needed.
However, mild to moderate side effects, such as diarrhoea, nausea and vomiting, were more common in the EloraTZP groups than those on tirzepatide alone or the placebo. This is probably why up to 27 per cent of those in the EloraTZP groups dropped out of the trial, whereas the dropout rate was just 3 per cent in the tirzepatide group and 17 per cent in the placebo group, says Preiss.
The increased risk of such side effects may put some people off the combined treatment approach, even if it carries the potential for greater weight loss, says Heisler. “They might find the combination more difficult to tolerate. If the patient’s already doing well on a drug like tirzepatide, then additional benefit may not outweigh the added treatment burden or side effects.”
What’s more, some people would only benefit from losing small or moderate amounts of body weight, and so EloraTZP may not be the right approach for them, says Preiss. Still, a larger trial of EloraTZP, delivered as a single weekly injection, is set to launch by the end of the year, the team wrote in a press release. If all goes smoothly, the US Food and Drug Administration could approve the approach for wider use in the next few years, says Heisler.
Although the latest trial was based on people with type 2 diabetes, weight-loss drugs consistently have larger effects in people who don’t have the condition, but have obesity or are overweight. It is unclear why this is the case, says Preiss, but it suggests the benefits of EloraTZP could be even greater for such people, although further trials are needed to verify this, he says.
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