Tirzepatide outperforms semaglutide in trial

A new study unveiled at this year’s European Congress on Obesity in Malaga revealed that tirzepatide delivers significantly greater weight loss than semaglutide in people living with obesity, but without diabetes.

Published in the New England Journal of Medicine, the 72-week phase 3b trial involved 751 adults and is the first of its kind to directly compare the two medications. Participants, mostly women with an average BMI of 39.4, received either tirzepatide (10mg or 15mg) or semaglutide (1.7mg or 2.4mg) via weekly injections.

By the end of the study, those treated with tirzepatide had lost an average of 20.2 per cent of their body weight – nearly 50 per cent more than the 13.7 per cent average loss seen with semaglutide. Waist circumference also reduced more with tirzepatide – by 18.4 cm versus 13.0 cm, a 42 per cent greater improvement.

Key findings showed tirzepatide users were significantly more likely to hit major weight loss milestones. Lead author Dr Louis Aronne from Weill Cornell Medicine explained that tirzepatide activates two receptors (GIP and GLP-1), while semaglutide only targets one (GLP-1), potentially accounting for the greater weight loss.

While both medications were generally well tolerated, gastrointestinal side effects were the most common, occurring mostly during dose increases. The study also found that men experienced around 6 per cent less weight loss than women, which may partly explain why weight loss in this trial was slightly lower than in earlier studies with fewer male participants.

Importantly, greater weight loss was linked to stronger improvements in cardiometabolic markers like blood pressure and cholesterol. Nearly two-thirds of tirzepatide users lost at least 15 per cent of their weight, and one-third achieved 25 per cent or more – a result that could offer substantial health benefits.

With waist circumference now recognised as a key risk factor – every 5 cm increase linked to higher mortality – the extra 5.4 cm average reduction seen with tirzepatide could prove life-saving.

Although the trial wasn’t blinded, the findings align closely with results from other blinded trials, lending confidence to their validity. The inclusion of a diverse participant group and use of maximum tolerated doses also strengthens the relevance of the results.

“This study confirms what we’re seeing in real-world practice,” said Dr Aronne. “Tirzepatide offers a new benchmark for weight reduction in people living with obesity.”