Sustained weight loss with personalized semaglutide dosing

A new study presented at the European Congress on Obesity (ECO) in Venice, Italy (12-15 May) investigated the benefits of personalised semaglutide dosing for patients on a weight loss programme and gradually tapering the drug once the target weight was reached. The study was conducted by researchers at Embla, a digital weight loss clinic based in both Copenhagen, Denmark, and London, UK, led by Dr Henrik Gudbergsen, Principal Investigator and Chief Medical Officer at Embla.

The study found that lower doses were as effective as higher doses, and that slowly tapering the dose with an emphasis on lifestyle changes prevented weight regain.

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

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

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

Researchers at Embla wanted to know whether it would be possible to tailor the dosage of semaglutide to minimise side effects while still achieving weight loss.

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

Personalization of semaglutide dosages

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

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

A standard dosing schedule, in which a starting 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), was adapted for each patient to minimize side effects.

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

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

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

During the programme, patients used about one-third of the amount of semaglutide used on the standard treatment schedule (36.1% of the proposed cumulative dose at week 64 and 34.3% at week 76).

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

Further analysis showed that weight loss was similar in patients regardless of their initial BMI or the 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, lead investigator and chief medical officer of Embla

Gradual reduction of semaglutide dosage

353 of 2246 patients (83% women, median age 49 years, median BMI 31.5, mean body weight 92 kg/14 st 7 lb) began a semaglutide taper once target weight was achieved. This involved gradually reducing the dose to zero over a median of nine weeks, while continuing to receive diet and exercise counselling (standard practice is to stop semaglutide abruptly when tapering is undertaken, which typically lasts between two and eight weeks).

The average weight loss over nine weeks of gradual reduction was 2.1%.

Of the 353 patients, 240 had their semaglutide dose tapered to zero. Data for 26 weeks after tapering to zero were available for 85 participants. Instead of gaining weight after stopping the drug, their weight remained stable (average weight loss was 1.5% after stopping the drug completely).

Forty-six of 240 patients restarted semaglutide after stopping. The median weight gain from stopping to restarting was 1.3%.

The researchers found that patients who gradually tapered their semaglutide dosage maintained stable weight over the first 26 weeks.

“The combination of lifestyle support and gradual dose 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 it abruptly, he may find it difficult to resist his desires. However, if he stops it 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 maintenance lifestyle changes throughout the program, which should aid in weight loss and maintenance.”