Is coming off semaglutide slowly the key to preventing weight regain?

Patients who tapered off the drug kept off lost weight for at least 6 months, Danish study finds

Lower doses of the drug as effective for weight loss as higher ones

*Please mention the European Congress on Obesity when using this story*

New research being presented at the European Congress on Obesity (ECO) in Venice, Italy (12-15 May) has explored the benefits of giving personalised doses of semaglutide to patients taking part in a weight loss programme and tapering them off the medication when they reach their target weight. The study is by researchers at Embla, a digital weight loss clinic based in both Copenhagen, Denmark and London, UK, led by Dr Henrik Gudbergsen, the lead researcher and Embla’s Chief Medical Officer.

It found that lower doses were just as effective as higher doses and that slowly reducing medication while focusing on lifestyle changes prevents weight regain.

Glucagon-like peptide-1 (GLP-1) receptor agonists such as semaglutide are highly effective at helping people lose weight. By mimicking the action of a hormone called GLP-1, they reduce appetite and feelings of hunger, slow the release of food from the stomach and increase feelings of fullness after eating.

However, they can cause side-effects such as diarrhoea, nausea, vomiting, dizziness and headaches and many patients quickly regain much of the weight they have lost after they stop taking the medication.

Recent research, however, indicates that patients who receive nutrition and exercise coaching and support tackling issues linked to emotional eating, for example, alongside their weight-loss medication, are less likely to regain weight. Some studies also indicate that coming off the medication slowly may help prevent weight regain.

The researchers at Embla were interested in whether it was possible to tailor dosage of semaglutide to minimise side-effects, while still achieving weight loss.

They also wanted to know if patients who tapered off semaglutide, by slowly reducing their dose to zero, regained weight after coming off it completely.

Personalising doses of semaglutide

The real-world cohort study involved 2,246 individuals in Denmark (79% female, median age 49 years, median BMI of 33.2, median body weight 97kg/15st 4lb) who were enrolled in a weight management programme run through the Embla app, available in Denmark and in the UK.

The programme included advice from a nutritionist on healthy eating, increasing exercise and overcoming the psychological barriers to weight loss, access to doctors, nurses and psychologists through the app and a course of the weight loss drug semaglutide (Ozempic or Wegovy). 

The standard dosing schedule, in which a low initial dose of semaglutide (0.25 mg once weekly for Ozempic and Wegovy) is increased every four weeks for 16 weeks to a maximum dose of 2 mg for Ozempic and 2.4mg for Wegovy (which the patient remains on until treatment ends), was tailored to individual patients to minimise side-effects.

Patients received the lowest effective dose and increases were only considered if they had stopped making progress. If they maintained a weekly weight reduction >0.5% of their body weight and experienced manageable levels of side-effects and hunger, they remained on the existing dose.  The average maximum dose of semaglutide was 0.77mg.

After 26, 64 and 76 weeks, 1,392, 359 and 185 patients, respectively, were still taking part in the programme.

Average weight loss was 14.8% (14.8kg/2st 4lb) at week 64 and 14.9% (14.9kg/2st 4lb) at week 76.

During the programme, the patients used around a third of the amount of semaglutide that is used on the standard treatment schedule (36.1% of the suggested cumulative dose at week 64 and 34.3% at week 76).

All 68 of the patients with a reported weight at week 64 lost >5% of their body weight and 58/68 (85.3 %) lost >10% of their baseline body weight.

Further analysis revealed patients’ weight loss was similar, regardless of their initial BMI or the total amount of semaglutide used.

Side-effects included nausea, vomiting and stomach ache but were mild and transient.

“Our results show that weight loss is achievable regardless of initial BMI and the amount of semaglutide used,” says Dr Gudbergsen.

“Using lower doses of semaglutide is cheaper for patients, results in fewer side-effects and helps ensure that stocks of the drug, which are still limited, go further.”

Tapering semaglutide

353 of the 2,246 patients (83% female, median age 49 years, median BMI 31.5, average body weight 92kg/14st 7lb) started to “taper off” semaglutide after they had reached their target weight.  This involved gradually reducing their dose to zero over an average of nine weeks, while still receiving coaching on diet and exercise (standard practice is to stop semaglutide abruptly, when tapering is carried out, it would typically be over two to eight weeks).

Average weight loss during the nine weeks of tapering was 2.1%.   

240 out of 353 patients tapered semaglutide to zero. Data from 26 weeks after tapering to zero was available for 85 participants. Rather than regaining weight after stopping the drug, their weight had remained stable (average weight loss of 1.5% after coming off the drug completely).

46 out of 240 patients restarted semaglutide after stopping. Average weight gain from cessation to restarting the drug was 1.3%.

The researchers conclude that patients who tapered off semaglutide maintained a stable body weight for the first 26 weeks.

“The combination of support in making lifestyle changes and tapering seems to allow patients to avoid regaining weight after coming off semaglutide.” says Dr Gudbergsen.

“A patient’s appetite returns when they stop taking the drug and if they stop taking it suddenly, they may find it hard to resist their cravings. However, if they stop slowly, and have expanded their awareness and understanding of healthy lifestyle behaviours and eating habits, their hunger and satiety will be more manageable, making it easier for them to maintain a healthy weight.

“Meanwhile, the lower maximum dose creates a bigger need for patients to engage whole-heartedly in supportive lifestyle changes throughout the programme, which should help with losing weight and with keeping it off.”