Triple-strength semaglutide produces larger weight losses in landmark trials, but questions remain over tolerance and access

A triple-strength, once-weekly injection of semaglutide produced substantially greater weight loss than the currently approved 2.4 mg dose in two large international randomized trials involving more than 2,000 adults with obesity, investigators reported.

Participants were randomly assigned to receive either 7.2 mg semaglutide, the standard 2.4 mg dose, or placebo injections alongside diet and exercise advice and were followed for 72 weeks. Among participants without diabetes, the 7.2 mg group lost an average of 18.7 percent of body weight, compared with 15.6 percent in the 2.4 mg group and 3.9 percent in the placebo group. Almost half of those on the higher dose lost at least 20 percent of their body weight, and nearly a third lost 25 percent or more.

Results among people with type 2 diabetes were smaller but still favored the higher dose: average weight loss was about 13 percent with 7.2 mg, 10 percent with 2.4 mg and just under 4 percent with placebo. Investigators reported additional benefits in waist circumference, blood pressure, cholesterol and blood-sugar control. In participants who began the trials with prediabetes, more than 80 percent of those taking 7.2 mg reverted to normal blood glucose levels by week 72.

Side effects were more frequent at the higher dose. Nausea, vomiting, diarrhoea and constipation were the most commonly reported adverse events. About one in five participants reported tingling or skin sensitivity. Most problems were described by the trial authors as mild to moderate and resolved over time. Approximately one in 20 participants discontinued treatment because of side effects, a rate similar to that seen with the approved 2.4 mg dose, and the studies did not find an increase in serious complications with the higher dose.

"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.

Not all specialists were persuaded broader use will follow. Professor Alex Miras, an obesity expert at Imperial College London, said the incremental benefit may be modest compared with the size of the dose increase and expressed concern about tolerability and cost. "Tripling the dose only gives a marginal extra benefit, but the dose increase is massive," he said. "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. In clinical practice people already struggle at 2.4 mg." He added that uptake could be limited by price and side effects and highlighted combination treatments in development that may deliver larger average losses.

Semaglutide belongs to a class of drugs known as GLP-1 receptor agonists, which mimic a gut hormone to reduce appetite and help regulate blood sugar. It is marketed as Ozempic for diabetes and Wegovy for weight management and has transformed treatment options for obesity in recent years, prompting strong demand and debate over access.

The trials' authors and outside experts noted several caveats. The studies ran for 72 weeks, and investigators said longer-term data will be needed to determine whether the additional weight loss with 7.2 mg is sustained and whether the safety profile remains stable with extended use. Any change in prescribing practice would require regulatory approval of the higher dose.

Access and cost issues have already shaped the rollout of weight-loss injections. Health-system and market pressures have driven changes in availability and price, and in the United Kingdom fewer than 200,000 people are estimated to be receiving weight-loss jabs through the National Health Service while an estimated 1.4 million use them privately, according to the King's Fund.

Researchers also noted ongoing development of combination therapies. Early data for a semaglutide-plus-cagrilintide formulation have suggested larger average weight losses than either semaglutide or other GLP-1 agents alone, a factor that some clinicians say could influence future treatment choices if confirmed in larger, longer trials.

Regulatory review, longer follow-up and real-world experience on tolerability and cost will determine whether the 7.2 mg semaglutide regimen becomes a widely available option for people who have not achieved sufficient weight loss on the currently approved dose.