Most weight-loss drugs do not meaningfully improve quality of life and few show improvements to heart health after a year, a new analysis has found
A systematic evidence review, published yesterday, reveals that most weight-loss drugs such as Wegovy and Mounjaro do not show ‘clinically important’ improvements in quality of life
Semaglutide injections (Wegovy) were the only drug associated with a reduced risk of death from heart attack (28%) or heart failure (57%), while tirzepatide (Mounjaro) also reduced heart failure risk by 51%, it found
No drug convincingly reduced kidney failure, according to the review published in the British Medical Journal (BMJ)
Compared with lifestyle changes alone – which saw people lose 2.5% of their body weight – the largest weight loss after one year was with tirzepatide (14.9%) and CagriSema (14.8%), followed by oral semaglutide (10.9%), orforglipron (9.9%), semaglutide injections (9.8%), and phentermine-topiramate (8.1%)
The analysis also said that emerging drugs such as retatrutide, ecnoglutide, and mazdutide showed ‘large effects’ on weight loss but were supported by low or very low certainty evidence
It also found that increased weight loss was generally accompanied by more severe side effects including stomach and bowel symptoms, fatigue, and loss of muscle mass, as well as treatment discontinuation
The researchers said this indicated a ‘clear benefit-harm trade-off’
The review was carried out by searching scientific databases for randomised controlled trials comparing one or more drugs with lifestyle changes, placebo, or another drug
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The researchers found 262 eligible trials involving 99,791 participants that evaluated 19 currently available and emerging weight-loss drugs with follow-up from 12 to 172 weeks
They acknowledged that most trials had relatively short follow-up periods, limiting their ability to draw conclusions about long-term safety, quality of life, and effect on heart and kidney health
The researchers found that benefits included changes in body weight, fat mass, and quality of life, while potential harms included changes in lean mass, gastrointestinal adverse events, gallbladder related disorders and fatigue
The authors concluded that ‘treatment decisions for obesity should be individualised, balancing expected benefits, harms, treatment burden, costs, availability, and patient preferences’
Dr Marie Spreckley, weight management researcher at the University of Cambridge, said: ‘This is a comprehensive and well-conducted systematic review and network meta-analysis that provides an important comparative overview of the rapidly evolving evidence on obesity medications
‘The findings do not show that obesity medications have no wider health benefits. Rather, they highlight that while the evidence for weight loss is strong, evidence for some longer-term outcomes is still developing and differs considerably between individual medications
‘This is particularly important for cardiovascular outcomes. Many weight-loss trials were not primarily designed or sufficiently long to assess outcomes such as heart attacks, heart failure or mortality
‘The absence of demonstrated benefit for all medications should therefore not be interpreted as evidence that these benefits do not exist.’
Professor Naveed Sattar, professor of cardiometabolic medicine at the University of Glasgow, said that additional large-scale trial data is needed before more definitive conclusions can be reached
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