STEP 2 shows smaller weight loss in people with type 2 diabetes

Results from STEP 2, a phase 3 trial of once-weekly semaglutide 2.4 mg in adults who have both type 2 diabetes and overweight or obesity, were published March 2, 2021. Participants on semaglutide 2.4 mg lost an estimated 9.6% of their body weight over 68 weeks, compared with 3.4% on placebo ^[1].

The trial enrolled adults with a body-mass index of at least 27 kg/m² and a glycated hemoglobin (HbA1c) of 7–10% (53–86 mmol/mol) who had been diagnosed with type 2 diabetes at least 180 days before screening ^[1]. Patients came from 149 outpatient clinics in 12 countries across Europe, North America, South America, the Middle East, South Africa, and Asia ^[1]. Between June 4 and Nov 14, 2018, 1,595 people were screened and 1,210 were randomly assigned in equal groups to semaglutide 2.4 mg (404), semaglutide 1.0 mg (403) — the dose approved for diabetes treatment — or a matching placebo (403), all given as a weekly injection for 68 weeks alongside a lifestyle program ^[1]. The study was double-blind and double-dummy, meaning neither patients nor investigators knew who got what ^[1].

What the numbers showed

The two co-primary endpoints were percentage change in body weight and the share of people losing at least 5% of body weight at week 68, comparing semaglutide 2.4 mg with placebo ^[1]. Estimated mean weight change was −9.6% (standard error 0.4) with semaglutide 2.4 mg versus −3.4% (0.4) with placebo, a treatment difference of −6.2 percentage points (95% CI −7.3 to −5.2; p<0.0001) ^[1].

On the second endpoint, 267 of 388 patients (68.8%) on semaglutide 2.4 mg reached at least 5% weight loss, versus 107 of 376 (28.5%) on placebo — an odds ratio of 4.88 (95% CI 3.58 to 6.64; p<0.0001) ^[1].

Side effects were more common on the drug. Adverse events of any kind were reported in 353 of 403 patients (87.6%) on semaglutide 2.4 mg, 329 of 402 (81.8%) on semaglutide 1.0 mg, and 309 of 402 (76.9%) on placebo ^[1]. Gastrointestinal adverse events — mostly mild to moderate, according to the investigators — occurred in 63.5% of the 2.4 mg group, 57.5% of the 1.0 mg group, and 34.3% of the placebo group ^[1].

The published abstract does not report the average weight change in the semaglutide 1.0 mg arm, or blood sugar results, so the size of the gap between the two active doses is not available from this source ^[1]. The trial was funded by Novo Nordisk and is registered as NCT03552757 ^[1].

Why it matters for patients

STEP 2 is the trial that tested semaglutide 2.4 mg specifically in people who have type 2 diabetes along with excess weight — a very common combination, and a group often excluded from or underrepresented in weight-loss studies. The headline figure of 9.6% average weight loss at 68 weeks gives a reference point for what happened in a controlled trial setting in this population ^[1].

Averages also hide a wide range of individual results. Roughly seven in ten people on the higher dose lost at least 5% of their weight, but that means about three in ten did not ^[1]. On placebo plus lifestyle support, more than one in four also hit the 5% mark, a reminder that structured diet and activity programs contributed to results in both groups ^[1].

The side-effect numbers are also concrete: nearly two-thirds of people on semaglutide 2.4 mg reported a gastrointestinal adverse event such as stomach upset, roughly double the rate on placebo ^[1]. The abstract describes these as mostly mild to moderate but does not break out how many people stopped treatment because of them ^[1].

This source does not compare STEP 2 with results from semaglutide trials in people without diabetes, so any statement about how much smaller the weight loss is in diabetes cannot be quantified from the material here.

What happens next

The trial is closed to new participants ^[1]. An accompanying commentary, "Semaglutide and effective weight control," was published online March 2, 2021, and appeared in The Lancet's March 13, 2021 issue ^[1]. Whether and how regulators weighed these specific results into labeling decisions is not addressed in this source.