Sustained weight loss with personalized semaglutide dosing

A new study presented at the European Congress on Obesity (ECO) in Venice, Italy (12-15 May) examined the benefits of personalized dosing of semaglutide for patients participating in a weight loss program and tapering the medication once target weight is achieved. The study was conducted by researchers from Embla, a digital weight loss clinic located in both Copenhagen, Denmark and London, UK, under the direction of Dr. Henrik Gudbergsen, principal investigator and chief medical officer of Embla.

The study found that lower doses were as effective as higher doses, and that slow dosage reduction with an emphasis on lifestyle changes prevented weight regain.

Glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide, are very effective in helping people lose weight. By imitating the action of the hormone GLP-1, they reduce appetite and hunger, slow down the release of food from the stomach and increase the feeling of fullness after eating.

However, they can cause side effects such as diarrhea, nausea, vomiting, dizziness and headaches, and many patients quickly regain much of the lost weight after stopping the medication.

Recent research, however, indicates that patients who receive nutrition and exercise counseling and support for emotional eating problems, for example, along with drug therapy, are less likely to regain weight. Some studies also suggest that gradually stopping the medication may help prevent weight regain.

Researchers at Embla wondered whether it was possible to tailor the dosage of semaglutide to minimize side effects while still achieving weight loss.

They also wanted to know whether patients gained weight after stopping semaglutide completely if they gradually tapered their dose to zero.

Personalization of semaglutide dosages

The real-life cohort study included 2246 people in Denmark (79% female, median age 49 years, median BMI 33.2, median body weight 97 kg/15st 4lb) who participated in a weight management program through the Embla app available in Denmark and Great Britain.

The program included advice from a nutritionist on eating healthy, increasing physical activity and overcoming psychological barriers to weight loss, access to doctors, nurses and psychologists through the app, and a course of taking the weight-loss drug semaglutide (Ozempic or Wegovy). p>

A standard dosing schedule in which an initial low 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 2.4 mg for Wegovy (which the patient takes until the end of treatment), has been adapted for each patient in order to minimize side effects.

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

At 26, 64, and 76 weeks, 1392, 359, and 185 patients, respectively, remained in the program.

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

During the program, patients used about a third of the amount of semaglutide used under the standard treatment schedule (36.1% of the suggested cumulative dose at week 64 and 34.3% at week 76).

All 68 patients who provided weight data at 64 weeks lost >5% of their body weight, and 58 of 68 (85.3%) lost >10% of their baseline body weight.

Further analysis showed that patients' weight loss was similar regardless of their initial BMI or total amount of semaglutide used.

Side effects included nausea, vomiting and abdominal pain, but were mild and temporary.

Our results show that weight loss is achievable regardless of initial BMI and the amount of semaglutide used.

Using lower doses of semaglutide is cheaper for patients, causes fewer side effects and helps ensure that supplies of the drug, which are still limited, are used more effectively.” — Dr. Henrik Gudbergsen, Principal Investigator and Chief Medical Officer of Embla

Gradually reducing the dosage of semaglutide

353 of 2246 patients (83% women, median age 49 years, median BMI 31.5, mean body weight 92 kg/14st 7lb) began tapering semaglutide after achieving target weight. This involved tapering the dose to zero over an average period of nine weeks, while continuing to receive advice on diet and exercise (standard practice is to abruptly stop taking semaglutide; when tapering is carried out, this usually lasts two to eight weeks).

The average weight loss over the nine-week taper was 2.1%.

240 of 353 patients reduced their semaglutide dosage to zero. Data for 26 weeks after reduction to zero were available for 85 participants. Instead of gaining weight after stopping the medication, their weight remained stable (average weight loss was 1.5% after stopping the medication completely).

46 of 240 patients resumed semaglutide after discontinuation. The average weight gain from discontinuation to resumption of medication was 1.3%.

The researchers concluded that patients who gradually reduced their dosage of semaglutide maintained stable weight during the first 26 weeks.

“The combination of lifestyle support and gradual dosage reduction allows patients to avoid weight gain after stopping semaglutide,” says Dr. Gudbergsen.

“The patient's appetite returns when he stops taking the drug, and if he stops abruptly, he may find it difficult to resist his urges. However, if he stops gradually and increases his knowledge and understanding of healthy habits and behaviors, his hunger and satiety will be more manageable, making it easier to maintain a healthy weight.

“Meanwhile, the lower maximum dose creates a greater need for patients to actively engage in supportive lifestyle changes throughout the program, which should aid in weight loss and maintenance.”