Semaglutide 2.4 mg cut weight 9.6% in adults with type 2 diabetes in STEP 2 trial

In a phase 3 trial published in The Lancet, adults with overweight or obesity and type 2 diabetes who took weekly semaglutide 2.4 mg injections lost an estimated 9.6 percent of their body weight over 68 weeks, compared with 3.4 percent for those taking a placebo ^[1].

The trial, called STEP 2, randomly assigned 1,210 patients to semaglutide 2.4 mg (404 people), semaglutide 1.0 mg (403 people) or placebo (403 people) at 149 outpatient clinics in 12 countries across Europe, North America, South America, the Middle East, South Africa and Asia. Screening ran from June 4 to Nov. 14, 2018. Participants had a body-mass index of at least 27 kg/m², a glycated hemoglobin (HbA1c) between 7 percent and 10 percent, and had been diagnosed with type 2 diabetes at least 180 days before screening. Everyone received a weekly injection plus a lifestyle intervention for 68 weeks, and patients, investigators and outcome assessors did not know who was getting which treatment ^[1].

The estimated difference in weight change between semaglutide 2.4 mg and placebo was −6.2 percentage points (95 percent confidence interval −7.3 to −5.2; p<0.0001) ^[1]. By week 68, 267 of 388 patients on the 2.4 mg dose (68.8 percent) had lost at least 5 percent of their body weight, compared with 107 of 376 on placebo (28.5 percent; odds ratio 4.88, 95 percent CI 3.58 to 6.64; p<0.0001) ^[1]. The trial also tested semaglutide 1.0 mg, described in the paper as the dose approved for diabetes treatment, but the published abstract does not report a weight-change figure for that group ^[1].

Adverse events were more frequent with semaglutide: 87.6 percent of patients on 2.4 mg (353 of 403) and 81.8 percent on 1.0 mg (329 of 402), compared with 76.9 percent on placebo (309 of 402) ^[1]. Gastrointestinal events, described as mostly mild to moderate, were reported by 63.5 percent of patients on 2.4 mg, 57.5 percent on 1.0 mg and 34.3 percent on placebo ^[1]. Novo Nordisk funded the trial, and the authors concluded that weekly semaglutide 2.4 mg produced a "superior and clinically meaningful decrease in bodyweight compared with placebo" in this population ^[1]. The study is registered as NCT03552757 and is closed to new participants ^[1].

Why it matters for patients

STEP 2 measured weight loss specifically in people who have type 2 diabetes, so it gives that group a direct number rather than an estimate borrowed from trials in other populations. The average result also hides a wide spread of individual outcomes: about three in ten patients on the 2.4 mg dose did not reach 5 percent weight loss, while 28.5 percent of those on placebo did ^[1].

Gastrointestinal side effects were roughly twice as common on the 2.4 mg dose as on placebo, though the trial reports most as mild to moderate. How many participants stopped treatment because of side effects is not reported in the published abstract, and the trial did not compare semaglutide against other GLP-1 medications or against tirzepatide, so how the drugs rank against each other is not answered here ^[1].

Eligibility required a BMI of at least 27 kg/m² and an HbA1c between 7 and 10 percent, so people outside those ranges were not studied ^[1]. The trial followed patients for 68 weeks and does not report what happened to weight after treatment stopped, whether weight was regained, or how the results compare with longer-term use ^[1].

What happens next

The STEP 2 trial is closed to new participants, and the paper does not describe further planned follow-up of this group ^[1]. No head-to-head trial of semaglutide 2.4 mg against other weight-management medications in people with type 2 diabetes is described in the published abstract ^[1].