CATEGORY: DIET & WEIGHT
If a weight-loss drug works at its approved strength, does tripling the dose do more? That was the question behind a 72-week trial of 1,407 adults with obesity. The answer was yes, by about three percentage points. An investigational weekly dose of semaglutide, 7.2 mg, reduced body weight an average of 18.7%, against 15.6% on the standard 2.4 mg dose and 3.9% on placebo.1 Nearly one in three people on the higher dose lost at least a quarter of their body weight. The extra came with more stomach trouble, and with an unfamiliar side effect: odd skin sensations such as tingling, rare at the standard dose and almost absent on placebo.
The Hormone Signal the Drug Imitates
Semaglutide imitates GLP-1, a gut hormone that tells the brain it has had enough and slows the stomach’s emptying. That is why people taking it feel satisfied with less food. The 2.4 mg weekly dose has been the approved strength for weight management for several years. Tripling it was the experiment.
Five on the High Dose for Every One Elsewhere
Allocation was random and hidden from everyone involved, participants and doctors alike. Across 95 clinics in 11 countries, 1,005 adults took the 7.2 mg dose, 201 took the standard 2.4 mg, and 201 took placebo, all with diet and activity counseling alongside, for 72 weeks. That is about a year and four months. Participants averaged 47 years old, and nearly three quarters were women. The headline figures count everyone randomized, whether or not they stayed on treatment, which makes them conservative rather than best-case.
The Gap Widened at the Far End
Between the two semaglutide doses the average difference was about three percentage points of body weight, 18.7% against 15.6%.1 At the extremes it widened. Losing more than a quarter of body weight happened for 31.2% on the higher dose and 15.3% on the standard one.2 Waistlines told the same story. The higher dose trimmed an average of 11.7 centimeters more than placebo, close to five inches, roughly the diameter of a grapefruit.
Nausea Rose With the Dose, and So Did Something New
Side effects climbed with the dose. Stomach complaints such as nausea, vomiting and constipation affected 70.8% on 7.2 mg, 61.2% on 2.4 mg and 42.8% on placebo. The less familiar finding was dysaesthesia, meaning abnormal skin sensations such as tingling or crawling, reported by 22.9% on the higher dose, 6.0% on the standard dose and 0.5% on placebo.1 Serious adverse events stayed uncommon and roughly even across groups. An accompanying editorial called the higher dose a real option for people who need more weight loss than the standard strength delivers, while cautioning that the average added benefit is modest and the side-effect burden clearly rises.2
The 7.2 mg dose is approved nowhere yet. Regulators will now weigh the added benefit against the added side effects. The trial itself tracked weight, waistlines and blood markers, not heart attacks, strokes or survival, which take longer studies to capture.
Key Takeaways
- Weekly semaglutide at 7.2 mg took off an average of 18.7% of body weight over 72 weeks, against 15.6% on the standard 2.4 mg dose and 3.9% on placebo.
- Twice as many people on the higher dose lost more than a quarter of their body weight, 31.2% against 15.3%.
- Side effects rose with the dose: roughly seven in ten had stomach complaints, and 22.9% reported unusual skin sensations such as tingling, against 0.5% on placebo. The higher dose is not approved anywhere, and the trial measured weight and related markers rather than long-term outcomes such as heart disease.
References
- Wharton S, et al. Once-weekly semaglutide 7·2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial. Lancet Diabetes Endocrinol. 2025;13(11):949–963. link
- Sattar N, Lean MEJ. Semaglutide 7·2 mg: another step towards defeating diseases mediated by obesity. Lancet Diabetes Endocrinol. 2025;13(11):901–903. link