Supervised exercise plus liraglutide kept more weight off a year after treatment, trial follow-up finds

The one-year follow-up of a randomized trial called S-LiTE, published in eClinicalMedicine in March 2024, found that adults with obesity who took the GLP-1 drug liraglutide while doing a supervised exercise program held onto more of their weight loss a year after all treatment stopped than those who took the drug alone ^[1][2].

The trial, run in Copenhagen, enrolled adults aged 18 to 65 with a body mass index of 32 to 43. All participants first completed an eight-week low-calorie diet and lost an average of 13.1 kg. They were then assigned 1:1:1:1 to one year of weight-loss maintenance with supervised exercise, once-daily injected liraglutide 3.0 mg, both combined, or placebo. Of the 166 people who finished that phase, 109 returned for the post-treatment assessment one year later ^[1].

What the follow-up found

Measured from randomization to one year after treatment ended, participants who had received exercise plus liraglutide weighed 5.1 kg less on average than those who had received liraglutide alone (95% confidence interval -10.0 to -0.2; P = 0.040). Their body-fat percentage was 2.3 points lower (-4.3 to -0.3; P = 0.026) ^[1].

More people who had the combination kept off at least 10% of their starting body weight from the start of the diet to one year after treatment ended than those who had taken placebo (odds ratio 7.2, 95% CI 2.4 to 21.3) or liraglutide alone (odds ratio 4.2, 95% CI 1.6 to 10.8). More people who had done supervised exercise alone kept off at least 10% than those who had taken placebo (odds ratio 3.7, 95% CI 1.2 to 11.1) ^[1].

During the year after treatment stopped, weight regain was 6.0 kg larger after ending liraglutide than after ending supervised exercise (95% CI 2.1 to 10.0), and 2.5 kg larger than after ending the combination (95% CI -1.5 to 6.5) ^[1].

The authors wrote that adding supervised exercise to obesity drug treatment appeared to improve healthy weight maintenance after treatment ended, and that weight and body composition held steady a year after supervised exercise stopped, in contrast to the regain seen after drug treatment alone ^[1]. The trial was funded by Helsefonden and the Novo Nordisk Foundation, and several authors report advisory board, lecture or research funding ties to Novo Nordisk, Eli Lilly, AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme and Sanofi ^[1].

Why it matters for patients

The drug tested was liraglutide 3.0 mg, a daily injection, not semaglutide (Ozempic, Wegovy, Rybelsus) or tirzepatide (Mounjaro, Zepbound). Whether the same pattern would appear with those medicines has not been reported.

The comparison is also a group average over a trial where everyone started from a diet-induced loss of 13.1 kg, which is not how most people begin treatment. The confidence interval for the main weight difference between the combination and liraglutide groups ran from about 10 kg in favor of the combination to nearly zero, meaning individual results varied widely ^[1]. The follow-up included 109 of the 166 people who finished the treatment phase; the analysis does not describe how those who returned differed from those who did not ^[1].

The exercise in the trial was supervised, which is more structure than most people have access to, and the published summary does not detail how often sessions were held or what they involved.

What happens next

No results beyond the one-year post-treatment visit have been reported. The trial is registered with ClinicalTrials.gov as NCT04122716 and with EudraCT as 2015-005585-32 ^[1]. The trial enrolled participants between Dec. 17, 2018, and Dec. 17, 2020 ^[1]. No follow-up beyond week 104, and no equivalent randomized test of exercise during semaglutide or tirzepatide treatment, has been reported.