Health & Wellbeing

What happens when you go off weight-loss drugs?

What happens when you go off weight-loss drugs?
Anti-obesity drugs alone may not be effective at maintaining weight loss
Anti-obesity drugs alone may not be effective at maintaining weight loss
View 1 Image
Anti-obesity drugs alone may not be effective at maintaining weight loss
Anti-obesity drugs alone may not be effective at maintaining weight loss

Next-gen anti-obesity drugs like injectable liraglutide, sold as Saxenda, deliver impressive results in the first 12 months. New research looks into what happens to those results once treatment stops.

The new generation of weight-loss medications has enjoyed a meteoric rise in popularity recently. Semaglutide started life as the antidiabetic drug Ozempic, but it was its potent bonus benefit that attracted worldwide attention. Rebranded as Wegovy, it quickly became the most successful weight loss drug in history.

Semaglutide was FDA-approved for weight management in 2021. However, it wasn’t the first GLP-1 weight loss drug to receive approval; that honor went to liraglutide (Saxenda) back in 2014. It’s just that, in comparison to the older weight loss drug, semaglutide seemed to hit a sweet spot in the public consciousness that, influenced by some celebrities admitting to taking it, resulted in global Wegovy shortages and helped make its manufacturer, Novo Nordisk, a US$500 billion company.

Clinical studies confirm the remarkable weight-loss abilities of GLP-1 drugs, fueling their popularity. But is this hype justified by clinical results? It’s interesting to note that both semaglutide and liraglutide were approved by the FDA for use in addition to a reduced-calorie diet and increased physical activity. Although there appear to be no studies addressing how many users are complying with the approved use of GLP-1 drugs, it’s unlikely that everybody who takes them has changed their diet and is exercising accordingly. Now, a couple of years on, researchers are re-examining the importance of exercise in combination with GLP-1 medications in the context of maintaining weight loss.

A series of five Semaglutide Treatment Effect in People with Obesity (STEP) trials, which Novo Nordisk funded, evaluated semaglutide’s efficacy as a weight-loss medication. The results of one trial, STEP 1, published in 2021, found that once-weekly semaglutide plus “lifestyle intervention” (read: diet and exercise) was associated with “sustained, clinically relevant reduction in body weight.” However, when a follow-up study, an extension of the STEP 1 trial also funded by Novo Nordisk, looked at what happened when treatment and lifestyle interventions were stopped, researchers found that, after a year, participants had regained two-thirds of their prior weight loss.

This brings us to the most recent study, led by researchers from the University of Copenhagen, Denmark, and just published in the journal eClinical Medicine. The researchers recruited 109 adults aged 18 to 65 with obesity and induced weight loss by having them eat a low-calorie diet for eight weeks. They were then allocated to one of four treatment groups to assess weight loss maintenance: supervised exercise alone, liraglutide alone, liraglutide plus exercise, or placebo.

A year after terminating the liraglutide-exercise combo, participants had reduced body weight and body fat percentage compared to those who terminated liraglutide alone. Those on the combination treatment maintained a weight loss of at least 10% of their initial body weight one year after ceasing the treatment compared with those who received liraglutide alone or a placebo. But, those who only exercised, not in combination with liraglutide, also maintained a weight loss of at least 10% compared to placebo. Moreover, weight regain after a year was 13 lbs/6.0 kg more for participants who’d received liraglutide alone compared with those who’d received exercise alone, despite similar initial weight loss. Needless to say, funding for the study was provided, in part, by Novo Nordisk.

“From our data, it is clear that those who followed an exercise regime with or without treatment with obesity drugs felt less tired and more energetic,” said Signe Sørensen Torekov, the study’s corresponding author. “They also experienced better mental health. It simply led to improved quality of life. The same did not apply to those who only received medical treatment. In fact, they felt more tired and less energetic.”

It's accepted that long-term adherence to weight loss treatment of any kind is challenging, and the results of the latest study suggesting that exercise is necessary for ongoing weight loss maintenance may, for some, increase the challenge factor. However, playing devil’s advocate for a moment, one must wonder whether the ‘quick-fix’ that GLP-1 weight loss drugs provide by themselves might be better achieved by way of dietary modifications and regular exercise, which appear to be effective, albeit slower in producing results.

It appears, though, that there’s no stopping this weight-loss train. In late 2023, the FDA approved Zepbound (tirzepatide), which can help people lose up to a whopping 50 lbs/23 kg. (The drug was already approved under the trade name Mounjaro for use as an antidiabetic treatment.) Dubbed the ‘King Kong of weight-loss drugs,’ it joins the expanding list of GLP-1 anti-obesity medications.

The reality is that diet drugs have been around for decades, and history is littered with a large collection of failures. Sibutramine, fenfluramine, dexfenfluramine, and so-called ‘rainbow diet pills’ containing amphetamines and diuretics have all been banned because they produce adverse cardiovascular effects. Rimonabant, too, for increasing suicide risk, and methamphetamine for increasing the likelihood of developing a drug dependence. Time will tell if the newest diet drugs are a fad or are here to stay.

Source: University of Copenhagen

I can't say I am surprised by the results. Exercise is beneficial for more than just burning calories it also transforms your body. Similar results are found when people diet for weight loss without exercise. You lose both fat and some muscle mass in calorie deficit and as soon as the diet ends the weight comes back. You are probably better off in the long run working out without dieting than you are dieting without working out and it seems like the same is true of weight loss drugs too. For me when I am working out everything else (more water intake, healthier higher protein eating habits etc.) tends to more naturally fall into place too. The less physically active I am the more I tend to reach for high sugar junk as a fuel source.
If you don't change the brain (thoughts, thought patterns, dependence on food-for-pleasure, tolerance of discomfort and even pain for doing healthy things), you can't change anything long-term.