Triple-strength semaglutide dose yields greater weight loss in landmark trials

Two international randomized trials involving more than 2,000 adults with obesity found that a triple-strength weekly dose of semaglutide — 7.2 milligrams — produced larger average weight loss than the currently approved 2.4 mg dose and markedly more than placebo over 72 weeks.

In participants without diabetes, those given the 7.2 mg injection lost an average of 18.7% of body weight by week 72, compared with 15.6% for the 2.4 mg dose and 3.9% for placebo combined with diet and exercise. Among people with type 2 diabetes, the higher dose yielded about 13% average weight loss, versus roughly 10% on the 2.4 mg dose and under 4% with placebo. Almost half of patients on the higher dose lost at least 20% of their body weight, and nearly a third lost 25% or more.

The trials randomly assigned adults with obesity, some of whom had diabetes, to receive weekly injections of semaglutide at 7.2 mg, 2.4 mg, or placebo alongside lifestyle advice. Investigators reported additional cardiometabolic benefits among those on the higher dose: reductions in waist circumference, improvements in blood pressure, cholesterol and blood glucose. Among participants with pre-diabetes, more than 80% of those taking 7.2 mg had reverted to normal blood sugar by week 72.

Side effects were more frequent at the higher dose. Nausea, vomiting, diarrhoea and constipation were the most common adverse events; about one in five participants reported tingling or skin sensitivity. Approximately one in 20 patients stopped treatment because of side effects, a discontinuation rate similar to the standard dose, and the studies did not show an increase in serious complications with 7.2 mg.

"Semaglutide 7.2 mg was well tolerated and provided additional clinically meaningful weight loss compared with 2.4 mg, suggesting that higher doses could help patients who do not achieve sufficient weight loss with the currently approved dose," the study authors wrote.

Experts not involved in the trials urged caution. Professor Alex Miras, an obesity specialist at Imperial College London, said tripling the dose produced only a modest additional benefit while substantially increasing the amount of drug patients would receive. "Going from 2.4 mg to 7.2 mg is a very big jump. I'm concerned many patients won't tolerate such a high dose," he said, adding that cost and side effects could limit uptake even if regulators approve the higher dose.

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist sold for diabetes as Ozempic and for weight management as Wegovy. The class has transformed obesity treatment and driven strong demand, prompting debate over access and cost. Reports have highlighted sharp price rises for the highest-dose pens for private patients in the UK, with costs cited as increasing from about £122 a month to more than £330, prompting negotiations between pharmacies and suppliers.

Industry and research attention is also focused on combination therapies. Early data on a semaglutide–cagrilintide combination, marketed as CagriSema, suggest average weight losses of around 23% in trials, greater than results reported for semaglutide alone or other agents in separate studies. Investigators and clinicians said longer-term follow-up will be needed to determine whether the greater weight loss with higher-dose semaglutide is sustained and to fully characterise safety over time.

Fewer than 200,000 people are estimated to be receiving weight-loss injections through the NHS in the UK, while more than 1.4 million are thought to be using them privately, according to the King's Fund. Any change in prescribing practice to allow a 7.2 mg dose would require regulatory approval and likely face consideration of clinical tolerance, cost, and equitable access.

The trial authors and independent experts said the higher dose could offer an option for patients who do not achieve sufficient weight loss on the approved dose, but cautioned that regulators, clinicians and patients will need evidence on longer-term benefits, safety and affordability before routine use could be recommended.