We’re in the middle of the obesity drug revolution, but a major review of hundreds of clinical trials has put a serious question mark over whether this new generation of therapies is delivering quality of life or heart health benefits in the long run.

A Chinese research team has published a review of data from 262 trials and close to 100,000 patients, demonstrating there’s little evidence to show obesity management drugs promote clinically significant improvements in quality of life at one year [link here].

They looked at data on 19 different therapies, comparing weight loss, adverse event, cardiovascular and kidney health outcomes for those on treatment compared with lifestyle modifications alone to manage obesity. Among their findings:

• Tirzepatide and cagrilintide-semaglutide resulted in the greatest weight loss (-14.9% for tirzepatide and 14.8% for CagriSema),
• The larger the weight loss benefit, the greater the magnitude of side effects, including gastrointestinal issues, fatigue and muscle loss,
• Semaglutide was the only therapy to show a reduction in all-cause mortality, MI and HF occurrence,
• No therapy showed a convincing reduction in kidney failure risk over the follow-up period, and
• No therapy showed an improvement in quality of life metrics at up to one year after the commencement of treatment.

Writing in BMJ, endocrinologist at West China Hospital Professor Sheyu Li and colleagues said their data confirmed many of the therapies do achieve substantial weight loss, but also highlighted a clear “benefit-harm” trade off when it came to adverse events.

They said treatment decisions should be focused keenly on the individual needs and goals, including the treatment burden and potential harms of starting on a therapy.

“Some patients may prioritise maximal weight loss, whereas others may place greater value on evident reductions in mortality or cardiovascular risk,” they said.

While the data did not show an overall benefit for cardiovascular health across all therapies, semaglutide did show a reduction in death, MI and HF occurrence, while tirzepatide also showed benefits for heart failure, the authors noted.

The researchers acknowledged most trials only had short-term follow up, however, which limited the conclusions that could be drawn about the long-term impacts of therapies on cardiovascular and renal health.

Data could guide patient choice 

Assistant Prof Hamlet Gasoyan

In an editorial on the paper, vice chair of research in primary care at The Cleveland Clinic Professor Michael Rothberg and assistant professor of medicine at Cleveland Clinic Hamlet Gasoyan agreed the short follow-up times for the studies made it hard to draw conclusions.

This limited the “ability to make robust assessments on the long term safety, quality of life, and effects on cardiovascular and kidney outcomes”, they said [link here].

Despite this, the analysis did provide insights into differences between treatments which could be important for patients.

“Physicians could use this up-to-date synthesis of evidence to guide their patients towards the treatments that are most suitable for them based on their preferences for outcomes and adverse events,” the editorialists said.

Using this data combined with information about drug availability and insurance coverage could help refine which of the many emerging obesity management options would work best for the patient in front of them.

While the study did not shed light on the long term quality of life benefits beyond mere weight loss, it was an “important step in providing comparative information to inform patient-clinician discussions about obesity drugs”, they said.