Tirzepatide Plus Eloralintide Yields 23% Weight Loss in Trial
Combining tirzepatide with the experimental drug eloralintide produced substantially greater weight loss than tirzepatide alone in a phase 2 trial of adults with type 2 diabetes, though side effects and dropout rates were higher.
Adding an experimental hormone-targeting drug to tirzepatide produced substantially greater weight loss than tirzepatide alone in a mid-stage clinical trial, according to results presented at the 62nd Annual Meeting of the European Association for the Study of Diabetes in Milan. Participants who received the highest dose of the combination lost about 23.3 per cent of their body weight on average over eleven months, compared with 14.8 per cent for those taking tirzepatide alone.
The trial, led by Dan Skovronsky of Eli Lilly in Indiana, recruited 367 adults from the United States and Argentina who were overweight or had obesity, all of whom also had type 2 diabetes. Participants were randomly assigned to receive either a 15-milligram dose of tirzepatide, varying doses of tirzepatide combined with eloralintide, or placebo injections. Eloralintide targets amylin, a third appetite-suppressing hormone, and was given as a separate weekly injection. The dual approach was named EloraTZP.
After eleven months, those on the highest dose of eloralintide plus tirzepatide lost an average of 24.5 kilograms, or 23.3 per cent of their body weight. The tirzepatide-only group lost 15.6 kilograms, or 14.8 per cent. The placebo group lost just 3 per cent of their body weight on average. Blood sugar reductions followed a similar pattern: 2.9 per cent in the high-dose combination group, 2.4 per cent with tirzepatide alone, and 0.3 per cent with placebo.
«It’s a pretty astonishing degree of weight loss,» said David Preiss of the University of Oxford, who was not involved in the research. Lora Heisler of the University of Aberdeen, also independent of the study, noted that adding an amylin-like drug «effectively brings a third appetite-regulating pathway into play, which may explain why the combination appears to deliver substantially greater weight loss.»
Tirzepatide, sold as Mounjaro and Zepbound, is currently the most potent approved weight-loss medicine. It mimics two appetite-suppressing hormones, GLP-1 and GIP, and is authorised in the UK, US, Europe and elsewhere for adults with type 2 diabetes or obesity, or those who are overweight with at least one weight-related condition such as high blood pressure. It is administered through weekly injections.
The combination approach, however, came with a higher burden of side effects. Mild to moderate gastrointestinal issues such as diarrhoea, nausea and vomiting were more common in the EloraTZP groups than with tirzepatide alone or placebo. Up to 27 per cent of participants in the combination groups dropped out of the trial, compared with 3 per cent in the tirzepatide-only group and 17 per cent in the placebo group.
Heisler suggested the increased risk of side effects may deter some patients. «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,» she said. Preiss added that some people only need to lose small or moderate amounts of weight, making the combination unnecessary for them.
Preiss also noted that the reductions in blood sugar and weight «would reduce the risk of cardiovascular complications, high blood pressure,» though he stressed that further studies exploring these outcomes are needed. The trial population had type 2 diabetes, but weight-loss drugs consistently show larger effects in people who have obesity or are overweight without diabetes. Preiss said it is unclear why this is the case, but it suggests the benefits of EloraTZP could be even greater for such people, pending verification in future trials.
A larger trial of EloraTZP, delivered as a single weekly injection rather than two separate shots, is set to launch by the end of the year, the team said. If results are favourable, Heisler suggested the US Food and Drug Administration could approve the approach for wider use within the next few years. The findings suggest that combining tirzepatide with an amylin-targeting drug could lead to more effective weight-loss therapies, an approach that may become available for broader clinical use in the coming years.
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