Weight regain after stopping GLP-1 drugs may plateau after time, researchers say

Although people appear to regain weight rapidly after taking GLP-1 weight-loss drugs this may plateau after time, a new modelling study has reported.

A year after stopping taking glucagon-like peptide 1 (GLP-1) receptor agonists like semaglutide (WeGovy) and tirzepatide (Mounjaro) people regain on average 60% of their lost weight, the latest analysis found.

But beyond this, their weight regain plateaus, with individuals managing to keep off 25% of the weight lost to treatment, researchers at the University of Cambridge have concluded.

It follows a paper earlier this year which found that weight regain after stopping GLP-1 medications is four times faster than after diet and exercise programmes.

The latest research is based on a model that extrapolates what happens in the longer-term after stopping taking weight-loss drugs.

Experts said their model was plausible but, data so far has come from clinical trials and it remains unclear what will happen in the real-world use of GLP-1 medications.

But it does underpin the view that patients may need to consider the drugs as part of long-term management of obesity as would happen with other chronic conditions.

The researchers also pointed out that it is not clear if weight regain constitutes both fat and muscle, or mainly fat.

Previous studies have suggested that lean body mass – including muscle – can constitute up to 40% of total weight lost during treatment.

While GLP-1 jabs have been shown in randomised controlled trials lead to weight loss of 15 to 20%, around half of all patients discontinue their use within the first year, with three-quarters stopping after two years.

Writing in Lancet title eClinicalMedicine, the team said they looked at evidence from 48 relevant studies, including 36 randomised controlled trials.

They honed in on six RCTs of more than 3,200 individuals that followed patients for up to 52 weeks after they stopped taking weight-loss drugs then developed a model to predict what would happen beyond that.

It estimated that at 60 weeks, weight regain starts to plateau and is projected to taper off at 75% of the original weight loss.

For an individual who had lost a fifth of their weight while on the drugs, this would correspond to a sustained weight reduction of around 5%, they concluded.

The trajectory appeared similar across types of weight-loss medication.

The researchers say there are several reasons why people may not return to their original weight even a year after stopping the medications, including that they have developed healthier eating habits, such as reduced portion sizes or more nutritionally balanced meals.

But the drugs may also alter hormone levels and ‘reset’ the brain’s appetite control mechanisms in the longer term.

Study author Steven Luo, from the School of Clinical Medicine and Trinity College, said: ‘When stopping weight-loss drugs, doctors and patients should be aware of the potential for weight regain and consider ways to mitigate this risk.

‘It’s important that people are given advice on improving their diet and exercise, rather than relying solely on the drugs, as this may help them maintain good habits when they stop taking them.’

Dr Marie Spreckley, researcher in prevention of diabetes and related metabolic disorders in high-risk groups at the MRC Epidemiology Unit at the University of Cambridge, said it was important to distinguish between observed data and projections and longer-term follow-up studies are now needed to confirm whether this plateau occurs in routine practice.

‘Obesity is widely recognised as a chronic, relapsing condition, so it is not unexpected that stopping pharmacotherapy is followed by partial weight regain in many individuals.

‘A decelerating trajectory is biologically plausible, but without multi-year empirical data we cannot be certain which projection most closely reflects long term real-world outcomes.’

But she added: ‘Overall, the study reinforces that GLP-1 receptor agonists are unlikely to produce durable weight loss if used as short term interventions without longer term management plans.

‘For many patients, they may need to be considered as part of ongoing treatment strategies alongside nutritional and behavioural support.’

A recent analysis suggested that one in ten British adults were either taking weight-loss drugs or had plans to do so in the near future.