Only one weight-loss jab shown to cut risk of death, landmark study finds

New findings suggest the majority of obesity treatments fail to produce meaningful improvements in quality of life

Oral versions of Wegovy perform as well as injectable forms for weight loss, though the tablets may not confer the same heart-protective effects, a major study published in the British Medical Journal has found.

While analysing all available evidence on weight-loss medications, researchers found that despite helping patients lose weight, the majority of obesity treatments, including Wegovy and Mounjaro, fail to produce meaningful improvements in quality of life.

The comprehensive review examined 19 obesity drugs currently on the market or in development, drawing on 262 studies involving nearly 100,000 participants. Follow-up periods ranged from 12 to 172 weeks across the trials.

When measured against lifestyle modifications alone, Mounjaro (tirzepatide) delivered the most substantial weight reduction at the one-year mark, with patients losing 14.9 per cent of their body weight.

A new injectable treatment called CagriSema came close behind at 14.8 per cent.

Oral semaglutide, marketed as Wegovy pills, achieved 10.9 per cent weight loss, while the experimental tablet orforglipron reached 9.9 per cent.

Injectable Wegovy produced a 9.8 per cent reduction, with phentermine-topiramate pills achieving 8.1 per cent.

Several emerging treatments, including retatrutide, ecnoglutide and mazdutide, demonstrated significant weight loss effects, though researchers noted these findings were backed by low or very low certainty evidence.

Mounjaro also led to the greatest reduction in body fat at 25.7 per cent, but this came with a significant trade-off: patients experienced the largest loss of lean body mass, including muscle, at 8.3 per cent.

The cardiovascular findings proved particularly noteworthy. Injectable Wegovy stood alone as the only medication associated with lower mortality risk from all causes, reduced by 19 per cent, alongside a 28 per cent decrease in heart attack risk and a 57 per cent reduction in heart failure.

Mounjaro showed a 51 per cent reduction in heart failure risk.

However, no drug demonstrated convincing evidence of preventing kidney failure, and greater weight loss correlated with increased side effects, including gastrointestinal problems.

The researchers, who included experts from China, Norway and Canada, acknowledged that most clinical trials featured relatively brief follow-up periods, which limits what can be concluded about long-term safety, quality of life impacts and effects on heart and kidney health.

The study authors stated: "Treatment decisions for obesity should be individualised, balancing expected benefits, harms, treatment burden, costs, availability and patient preferences."

In an accompanying editorial, physicians from the Cleveland Clinic in Ohio described the research as "an important step in providing comparative information to inform patient-clinician discussions about obesity drugs in this rapidly evolving landscape of treatment options".