Weight Loss Maintained With Slow Taper of Semaglutide

VENICE, ITALY — Personalized doses and slow tapering of semaglutide (Wegovy or Ozempic, Novo Nordisk) in patients who also follow a digital weight loss program can lead to maintenance of target weight up to 6 months later, show retrospective, real-world data.

Lower doses were found to be just as effective as higher doses for weight loss. Slowly reducing medication while focusing on lifestyle changes using a digital program seemed to help prevent weight regain, said the study lead Henrik Gudbergsen, MD, lead researcher and chief medical officer at Embla, a digital weight loss clinic, in Copenhagen, Denmark.

Patients in the weight loss program used around a third (36.1%) of the suggested cumulative semaglutide dose and lost a median of 14.8% (95% CI, 14.3%-15.2%) of body weight by week 64. Sideeffects included nausea, vomiting, and stomachache, but were mild and transient.

“It’s the same amount of weight loss seen in the phase 3 trials [of semaglutide], so individuals also lose roughly 15% of the weight they have when they join our program but with a third of the medication. The lifestyle modifications actually work,” Gudbergsen told Medscape Medical News.

Of those patients who tapered off semaglutide to zero — data are available for 85 participants — a stable body weight was maintained for the first 26 weeks.

The work is being presented as two posters on 13 and 14 May at the European Congress on Obesity (ECO) 2024.

“Our results show that weight loss is achievable regardless of initial body mass index (BMI) and the amount of semaglutide used,” said 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.”

Reflecting on the continued small weight loss after stopping, Gudbergsen said, “The combination of support in making lifestyle changes and slow tapering seems to allow patients to avoid regaining weight after coming off semaglutide. I think that’s testament to the fact that they actually have learned more about emotional eating behaviors, lifestyle, food, exercise, and so on, and not just relied on semaglutide for the weight loss. They’re actually in control.”

Gudbergsen also noted that the lower maximum dose facilitated engagement with supportive lifestyle changes throughout the program that “should help with losing weight and with keeping it off.”

Weight Loss Without Side Effects

Gudbergsen and his colleagues at Embla wanted to find out if semaglutide could be tailored to achieve weight loss with minimal side effects, as well as determining, whether once the target weight was achieved, the drug dose could be slowly tapered to zero without weight regain.

A total of 2246 individuals living with obesity (BMI ≥ 30) or overweight with at least one weight-related comorbidity (BMI between 27 and 29.9) were included in the study. All participants lived in Denmark, and the median age was 49 years (41-55 years), and the median BMI was 33.2. They were all enrolled in the Embla digital weight loss app program.

As a weight loss program, Embla comprises a combination of weight loss medication and lifestyle changes supported by nurses, doctors, health coaches, and a psychologist, while Embla communities support each other.

Participants received a tailored version of the standard semaglutide dosing schedule (starting at 0.25 mg once weekly, with 4-weekly incremental increases to 2 mg maximum for Ozempic and 2.4 mg for Wegovy) to ensure the lowest effective dose that accommodated any side effects. Doses were increased if weight loss stagnated, but if a weekly weight loss of at least 0.5% of body weight was achieved, then the dose remained the same. The tapering plan involved slowly reducing the medications over a median of 9 weeks.

Weight Loss Maintained After Stopping Semaglutide — Small Numbers

After 26, 64, and 76 weeks, a total of 1,392, 359, and 185 participants remained in the program, respectively (median overall follow-up time was 32 weeks for the 2246 individuals who started the program).

The average maximum dose of semaglutide was 0.77 mg, and all participants with a reported weight at week 64 lost over 5% of their body weight, and 85.3% lost over 10% of their baseline body weight. There was no difference in the amount of weight loss achieved according to baseline BMI and/or cumulative dose of semaglutide.

In the 353 participants who tapered their semaglutide dose, the median duration of the tapering was 9 weeks (95% CI, 8%-10%), after which time the median change in body weight was −2.1% (95% CI, −3.5% to −0.8%). Nearly 40% began tapering after 72 weeks on the program.

A total of 240 patients (of 353) stopped the drug completely, and available data from 85 of these participants showed an average body weight loss of −1.5% (95% CI, −6.4% to 3.3%) at 26 weeks after stopping. The median follow-up time after stopping was 19.5 weeks.

“Because they’ve engaged in some of the lifestyle changes, when they eventually taper off, they keep the weight off without semaglutide,” said Gudbergsen. “I think there’s a strong linkage between the initial phase of using this medication with lifestyle changes and actually being capable of keeping the kilos off once they’ve stopped.”

Of the 46 participants who restarted semaglutide, body weight had increased since stopping by 1.3% (95% CI, −0.1% to 2.7%), and the probability of restarting was 21.5% (95% CI, 14.8-27.6%) 26 weeks after stopping semaglutide.

Asked to comment on the work, Esben Selmer Buhl, MD, PhD, general practitioner physician, Institute for Health and Society, University of Oslo, Oslo, Norway, said, “We know from other studies that after a major weight loss — regardless of the regimen used — the weight adjusted metabolic rate is reduced by approximately 25%, and the patient’s ability to feel satiety is vastly impaired while the feeling of hunger is vastly upregulated,” he explained, adding that, “Studies also suggest this situation persists for years in those very few who are able to maintain their weight for a long time after a major weight loss.”

Having to deal with a reduced basal metabolic rate in addition to being hungrier than ever explains why sustained weight loss is difficult over time. “I am skeptical that tapering off semaglutide will fundamentally change these circumstances. I believe the majority of patients in Embla’s study would begin to regain weight at some point, after being left on their own, and this corresponds to my clinical experience.”

“We’ve tried reducing or even tapering off semaglutide, but at some point — usually within 3-18 months — all patients will start regaining weight, and we’ve found that our patients need repeated treatment cycles to maintain body weight. Many patients prefer permanent sematglutide treatment to secure weight maintenance to reduce the risk of yo-yo weight cycling.”

“Nevertheless, not least due to the costs for semaglutide, lower-dose semaglutide, for instance, 1.0 mg per week in addition to diet and exercise, seems to be a sweet spot for maintaining the weight lost,” said Selmer Buhl.

Gudbergsen is an employee of Embla and has company stock. Selmer Buhl is a former employee of McKinsey & Company 2010-2011 (serving clients within pharma I cannot disclose) and Novo Nordisk (2011-2016) (Head of Medical Affairs, NN Scandinavia, region Denmark). Dr Halford has received research funding from the American Beverage Association.

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