Semaglutide 7.2 Mg In Obesity: Step Up Trial Readout

Key Takeaways

• Semaglutide 7.2 mg was associated with greater week 72 weight loss than semaglutide 2.4 mg and placebo.
• Higher-dose treatment was also associated with more participants reaching larger weight-loss thresholds and with reduced waist circumference versus placebo.
• Gastrointestinal adverse events and dysaesthesia were more common with 7.2 mg, serious adverse events occurred in all groups, and the investigators described the overall risk-benefit profile favorably.

Once-weekly semaglutide 7.2 mg was associated with a mean bodyweight change of -18.7% at week 72 in adults with obesity and no diabetes, exceeding the reductions seen with semaglutide 2.4 mg and placebo in this randomized comparison. Participants had BMI 30 kg/m2 or greater and received treatment alongside lifestyle intervention. The higher dose also showed a different tolerability pattern during follow-up.

The STEP UP trial was a phase 3b, randomized, double-blind, placebo-controlled and active-controlled study conducted across 95 hospitals, specialist clinics, and medical centers in 11 countries. Adults with BMI 30 kg/m2 or greater and no diabetes were assigned 5:1:1 to once-weekly subcutaneous semaglutide 7.2 mg, semaglutide 2.4 mg, or placebo, all with lifestyle intervention, for 72 weeks. The randomized sample included 1407 participants, with 1005, 201, and 201 in the respective groups. Women accounted for 73.7% of participants; mean age was 47 years, mean bodyweight was 113.0 kg, and mean BMI was 39.9 kg/m2. Coprimary endpoints were percentage change in bodyweight and the proportion achieving at least 5% bodyweight reduction for semaglutide 7.2 mg versus placebo at week 72.

At week 72, mean bodyweight change was -18.7% with semaglutide 7.2 mg, -15.6% with semaglutide 2.4 mg, and -3.9% with placebo. The estimated treatment difference for 7.2 mg versus 2.4 mg was -3.1% with a 95% CI of -4.7 to -1.6. The estimated treatment difference for 7.2 mg versus placebo was -14.8%, with a 95% CI of -16.2 to -13.4. Both comparisons had p values below 0.0001. The higher dose separated from both comparator groups on the primary weight-loss outcome.

Secondary efficacy measures followed the same pattern. Semaglutide 7.2 mg increased the odds of reaching 5%, 10%, 15%, 20%, and 25% bodyweight reduction versus placebo. The odds ratio for at least 5% weight loss versus placebo was 12.1, with a 95% CI of 8.3 to 17.6 and p<0.0001. Compared with semaglutide 2.4 mg, the 7.2 mg dose was also superior at the 20% threshold, with an odds ratio of 1.8, and at the 25% threshold, with an odds ratio of 2.4. Waist circumference also improved versus placebo, with an estimated treatment difference of -11.7 cm, a 95% CI of -13.0 to -10.4, and p<0.0001. These findings were consistent with the primary efficacy results.

Gastrointestinal adverse events were more common with semaglutide 7.2 mg than with semaglutide 2.4 mg or placebo. The rates were 70.8%, 61.2%, and 42.8%, respectively. Dysaesthesia was also more common with the higher dose, occurring in 22.9%, 6.0%, and 0.5% of participants across the three groups. Serious adverse events occurred in all groups, affecting 6.8% with semaglutide 7.2 mg, 10.9% with semaglutide 2.4 mg, and 5.5% with placebo. The investigators concluded that semaglutide 7.2 mg was superior to placebo and 2.4 mg for bodyweight reduction while retaining a favorable risk-benefit profile.