STEP UP T2D reports 13.2% weight loss at the 7.2 mg dose in diabetes

A randomized, controlled trial called STEP UP T2D found that a 7.2 mg weekly dose of semaglutide led to an average 13.2% reduction in body weight among adults with obesity and type 2 diabetes, compared with a 3.9% reduction on placebo, a difference of 9.3 percentage points ^[1]. The trial also found the higher dose lowered blood sugar, cutting HbA1c by 1.5 percentage points more than placebo ^[1].

The study enrolled 512 adults across sites in Bulgaria, Canada, Hungary, Poland, Portugal, Slovakia, South Africa, and the United States between January and May 2023 ^[1]. Participants were randomly assigned in a 3:1:1 ratio to receive semaglutide 7.2 mg, semaglutide 2.4 mg, or placebo for 72 weeks, all alongside lifestyle counseling ^[1]. About 52% of participants were female, the average age was 56, average starting weight was about 110 kilograms, and average HbA1c at the start was 8.1% ^[1].

Semaglutide 2.4 mg is the dose already approved in the United States for chronic weight management, sold under the brand name Wegovy. The trial's investigators noted that many people with obesity and type 2 diabetes do not reach their weight-loss goals on that dose, which is why the higher 7.2 mg dose was tested ^[1]. On the secondary measures, the 7.2 mg group was far more likely than the placebo group to lose at least 5%, 10%, 15%, or 20% of body weight, with odds ratios ranging from 8.1 to 12.3 depending on the threshold ^[1]. Waist circumference also dropped more on the higher dose, by 6.5 centimeters compared with placebo ^[1].

Side effects followed a familiar pattern for GLP-1 drugs but were more frequent at the higher dose. Gastrointestinal events, such as nausea or diarrhea, were reported by 53.1% of people on 7.2 mg, 51.5% on 2.4 mg, and 25.5% on placebo ^[1]. Serious adverse events occurred in about 9% of participants across all three groups, showing no clear increase from the higher dose ^[1]. One notable difference was dysaesthesia, an abnormal skin sensation such as tingling or burning, which was reported in 18.9% of people on 7.2 mg versus 4.9% on 2.4 mg and none on placebo ^[1]. Low blood sugar events serious enough to need help were rare and similar across all three groups ^[1].

Why it matters for patients

For people with both obesity and type 2 diabetes, the standard 2.4 mg semaglutide dose does not always produce enough weight loss to meet treatment goals ^[1]. This trial suggests a higher, 7.2 mg dose could offer substantially more weight loss and better blood sugar control for this specific group. But the tradeoff appears to be more gastrointestinal side effects and a much higher rate of dysaesthesia, an unusual and not fully explained finding that showed up almost only in the highest-dose group ^[1].

It is not yet known whether the 7.2 mg dose will be submitted for or receive approval from the Food and Drug Administration, what it might cost, or how it would be marketed alongside existing Ozempic and Wegovy products. The sources provided do not address regulatory timelines, pricing, or insurance coverage for this dose.

What happens next

The trial, registered as NCT05649137, is now closed and completed, with results published in Lancet Diabetes & Endocrinology ^[1]. A correction to the published article was later issued, though the nature of that correction is not detailed in the available source ^[1]. The study was funded by Novo Nordisk, the maker of semaglutide ^[1]. What regulatory steps, if any, will follow this trial is not established in the sources reviewed.