A major scientific review published in the British Medical Journal has concluded that weight loss injections and pills do not meaningfully increase quality of life. The study, the largest of its kind, analyzed 262 trials involving 100,000 participants with an average age of 49.
No Meaningful Improvement in Wellbeing
Researchers used questionnaires to establish quality of life scores. On average, after one year, people taking the drugs showed no meaningful improvement compared to those relying on lifestyle changes alone. The more weight individuals lost, the higher the risk of side effects such as stomach problems and muscle wastage. These side effects also increased the likelihood that patients would stop taking the medication.
Scope of the Review
The review examined 19 currently available and emerging obesity drugs, with participants followed for 12 to 172 weeks. Compared with lifestyle changes alone, the largest weight loss after one year was with Mounjaro at 14.9% and the new jab CagriSema at 14.8%. This was followed by Wegovy pills at 10.9%—which began being sold in the UK this week—orforglipron pills at 9.9%, and injectable Wegovy at 9.8%.
Limited Health Benefits
Few drugs appeared to improve heart health during the study period, and none convincingly reduced the risk of kidney failure. Lead researcher Sheyu Li of Sichuan University in China stated: “Larger benefits are generally accompanied by greater harms, treatment burden, and discontinuation. Weight loss improvements are not sustained after treatment cessation. Treatment decisions for obesity should be individualised, balancing expected benefits, harms, treatment burden, costs, availability, and patient preferences.”
Mechanism and Side Effects
GLP-1 drugs slow digestion and reduce appetite by mimicking the hormone glucagon-like peptide 1, which regulates hunger and fullness. They can cause side effects such as vomiting and require personalised support from specialists to maintain weight loss. The NHS prescribes Mounjaro and Wegovy for weight loss, but Ozempic only for diabetes. Researchers stressed that people taking these drugs must increase exercise levels substantially to prevent muscle wastage. Previous studies have shown that a large proportion of weight lost is muscle and bone density.
Muscle Loss and Exercise
Experts say weight-bearing exercise programmes are essential to minimise muscle loss. Stopping GLP-1 drugs usually results in fat returning, but not muscle or bone mass. Mounjaro caused the highest fat loss at 25.7% but also the largest loss of lean body mass, such as muscle, at 8.3%.
Exceptions and Emerging Drugs
Wegovy injections were the only drug linked to a lower risk of death from any cause, with users being 19% less likely to die during the study period. They were also 28% less likely to have a heart attack and 57% less likely to develop heart failure. Mounjaro reduced the heart failure risk by 51%. Emerging drugs such as retatrutide, ecnoglutide, and mazdutide showed large effects on weight loss but were supported by low or very low certainty evidence.
Limitations and Expert Commentary
The researchers from China, Norway, and Canada noted that due to relatively short follow-up periods, some benefits may not have been captured. Dr. Hamlet Gasoyan of the Cleveland Clinic in the US wrote in an accompanying editorial: “The growing number of new obesity drugs is welcome news for clinicians and over a billion people worldwide living with obesity or overweight as they expand the options for treatment. As the number of new drugs increases, physicians must now choose the right obesity treatment for each patient, individualising the balance of benefits and adverse effects.”
