A study published in The BMJ reveals that most obesity medications do not significantly improve quality of life and few show cardiovascular benefits.

In an article by Ingrid Torjesen, a journalist at the British Medical Journal, published on The BMJ website, she explains that drugs used to treat obesity , such as semaglutide (Wegovy) and tirzepatide (Mounjaro), while producing substantial weight loss in patients, do not significantly improve their quality of life, and most show no cardiovascular benefits after one year, according to a meta-analysis of the most recent trial data.

Torjesenm describes that, according to the findings in this new analysis, he discovered that drugs used for obesity that are “associated with greater weight loss were also generally associated with greater harms, including gastrointestinal symptoms, fatigue and loss of lean muscle mass, and had a higher likelihood of being discontinued by patients.”

Torjesenm also points out that the weight loss achieved when people took the medications “was not maintained after discontinuing treatment.”

As the journalist continues in the British Medical Journal, “previous meta-analyses had focused on weight loss outcomes, and obesity drugs had not been directly compared in head -to-head trials , leaving uncertainty about the broader balance of benefits and harms, thus prompting this meta-analysis.”

According to Torjesenm, the trials included in this analysis were essentially designed to “assess weight loss,” so the researchers felt it was necessary to conduct “longer-term trials to better determine the effects of obesity drugs on cardiovascular, renal, and other important outcomes.”

The authors who conducted this new analysis evaluated 19 drugs against obesity, both those already available to the public and the most recent ones.

The study involved 99,791 volunteers who were monitored for a period of between 12 and 172 weeks in order to determine the benefits of “weight loss”, as well as “fat mass loss” and “improvement in quality of life”, as well as “damages such as lean mass loss, gastrointestinal adverse events, gallbladder-related disorders and fatigue”, explains Torjesenm.

The authors found that “tirzepatide and the cagrilintide-semaglutide combination produced the greatest weight loss after one year, at 14.9% and 14.8%, respectively,” while oral semaglutide (10.9%), orforglipron (9.9%), subcutaneous semaglutide (9.8%), and phentermine-topiramate (8.1%) produced the greatest weight loss, Torjesenm notes.

Emerging drugs, including retatrutide, ecnoglutide, and mazdutide, showed large effects on weight loss, but are supported by low- or very-low-certainty evidence.

None of the drugs analyzed managed to “convincingly reduce the risk of kidney failure” nor did they “show clinically important improvements in quality of life”.

On the contrary, the research revealed that drugs used to combat obesity and “produced greater weight loss” were linked to “higher rates of side effects and treatment discontinuation,” explains Torjesenm; “which indicates a clear trade-off between benefit and harm,” the researchers assert.

In the authors’ opinion, “treatment decisions for obesity should be individualized, balancing expected benefits, harms, treatment burden, costs, availability, and patient preferences,” and they go on to explain that “some patients may prioritize maximum weight loss, while others may place greater value on clear reductions in mortality or cardiovascular risk.”

José M. Ordovás, from the USDA Jean Mayer Research Center on Human Nutrition and Aging (United States), told Science Media Centre that this new research “fits with what we already knew: some drugs produce significant weight loss, but losing weight does not automatically mean improving all aspects of health. The scale tells part of the story, but not the whole one.”

Marie Spreckley, a weight management researcher at the University of Cambridge who was not involved in the study, explained, “The findings do not show that obesity medications lack overall health benefits. Rather, they highlight that while the evidence for weight loss is strong, the evidence for some longer-term outcomes is still developing and varies considerably between individual medications.”

“This is particularly important for cardiovascular outcomes. Many weight-loss trials were not primarily designed for, or long enough to assess, outcomes such as heart attacks, heart failure, or mortality. Therefore, the absence of a proven benefit for all medications should not be interpreted as evidence that these benefits do not exist,” Spreckley concludes.

According to Naveed Sattar, who is a professor of cardiometabolic medicine at the University of Glasgow, and who also did not participate in the study, “we now have consistent evidence from multiple large-scale cardiovascular outcome trials of GLP-1 receptor agonists in type 2 diabetes, including semaglutide (both injectable and oral formulations), dulaglutide, albiglutide, and efpeglenatide, demonstrating reductions in major cardiovascular events compared with placebo.”

“There is already considerable evidence that many people experience significant improvements in their well-being that are not adequately reflected in traditional patient-reported outcome measures. This may help explain why millions of people worldwide are willing to pay for these medications out of their own pockets, while comparatively few would do so for treatments such as statins or antihypertensive drugs,” Sattar adds.