Study flags rapid return of weight, heart risks after obesity drugs

WASHINGTON, D.C.: Stopping weight-loss medications often leads to a gradual reversal of both weight and metabolic health gains, with most benefits fading within two years, according to an extensive new analysis of existing studies.

Researchers who reviewed data from 37 clinical studies involving 9,341 overweight or obese patients found that, on average, people regained nearly one pound (0.4 kg) per month after discontinuing weight-loss drugs. Based on that pace, participants were projected to return to their pre-treatment weight within about 1.7 years.

Improvements in key cardiovascular risk factors did not last much longer. Measures such as blood pressure and cholesterol levels, which had improved while patients were on medication, were projected to return to baseline within an average of 1.4 years after treatment stopped, according to findings published in The BMJ.

About half of the patients in the analysis had been treated with GLP-1 receptor agonists, including newer and more potent drugs such as semaglutide — sold as Ozempic and Wegovy by Novo Nordisk — and tirzepatide, marketed as Mounjaro and Zepbound by Eli Lilly. Among the 1,776 patients who received these newer medicines, weight regain was faster, averaging nearly 1.8 pounds (0.8 kg) per month after stopping treatment.

"But because people on semaglutide or tirzepatide lose more weight in the first place, they all end up returning to baseline at approximately the same time," said Dimitrios Koutoukidis of Oxford University, the study's senior researcher. That timeframe was roughly 1.5 years for patients who had taken the newer GLP-1 drugs, compared with about 1.7 years for those who stopped any type of weight-loss medication.

The researchers also found that, regardless of how much weight patients initially lost, monthly weight regain tended to be faster after stopping drug-based treatments than after discontinuing behavioral weight-management programs.

Because the analysis was retrospective — drawing on previously published studies rather than following patients forward in time — it could not determine why some individuals might maintain weight loss better than others.

"Understanding who does well and who does not is a bit of a ‘holy grail' question in weight-loss research, but nobody has the answer to that yet," Koutoukidis said.

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