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Randomized controlled trial

STEP UP T2D: semaglutide 7.2 mg in obesity with type 2 diabetes

At 72 weeks, weight had changed by −13.2% with semaglutide 7.2 mg and by −3.9% with placebo (difference of −9.3 percentage points; 95% CI, −11.0 to −7.7).

Lingvay I et al. Once-weekly semaglutide 7·2 mg in adults with obesity and type 2 diabetes (STEP UP T2D): a randomised, controlled, phase 3b trial. The Lancet Diabetes & Endocrinology, 2025. DOI: 10.1016/S2213-8587(25)00225-6

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Key facts

Drug
semaglutide
Design
Randomized controlled trial
Participants
512
Duration
72 weeks
Funding
Novo Nordisk
Registry
NCT05649137
Population
512 adults with obesity (BMI of 30 or more) and type 2 diabetes (HbA1c of 7.0 to 10.0%), at 68 sites in Bulgaria, Canada, Hungary, Poland, Portugal, Slovakia, South Africa and the United States, randomized to semaglutide 7.2 mg (307), semaglutide 2.4 mg (103) or placebo (102); 51.8% women, mean age 56 years, mean weight 110.1 kg, mean BMI 38.6 and mean HbA1c 8.1%.
Primary outcome
Percentage change in weight and share of participants who lost at least 5% at 72 weeks with semaglutide 7.2 mg once weekly versus placebo, both with a lifestyle intervention.

What it found

At 72 weeks, weight had changed by −13.2% with semaglutide 7.2 mg and by −3.9% with placebo (difference of −9.3 percentage points; 95% CI, −11.0 to −7.7). Compared with placebo, HbA1c fell by 1.5 points more (95% CI, −1.8 to −1.2) and waist circumference by 6.5 cm more (95% CI, −9.0 to −4.1). Digestive adverse effects affected 53.1% on 7.2 mg, 51.5% on 2.4 mg and 25.5% on placebo, and dysesthesia (altered skin sensations, such as tingling) 18.9%, 4.9% and no one, respectively. Level 2 or 3 hypoglycemia was uncommon and similar between groups.

Limitations

Funded by Novo Nordisk. The primary objective compared 7.2 mg with placebo, not with 2.4 mg, and the 2.4 mg group was small (103 versus 307). All participants received a lifestyle intervention. In 2026 the journal corrected some values in the paper's tables, figures and an appendix (baseline triglycerides, p values and some confidence intervals); none affects the figures cited here, which come from the abstract.

What it means for you

In people with obesity and type 2 diabetes, weekly semaglutide 7.2 mg reduced weight by an average of 13.2% over 72 weeks, compared with 3.9% on placebo, and it also lowered HbA1c. Dysesthesia (tingling or other altered skin sensations) was more common than with 2.4 mg, and the trial was not designed to compare the two doses with each other. Each person’s dose is decided by their doctor, who can also tell you which doses are authorized where you live.

Further reading

Related trials

  • semaglutide68 weeks

    STEP 2

    In people with type 2 diabetes, semaglutide 2.4 mg once weekly reduced weight by 9.6% at 68 weeks, compared with 3.4% on placebo.

  • semaglutide72 weeks

    STEP UP

    At 72 weeks, weight changed by −18.7% with semaglutide 7.2 mg, −15.6% with 2.4 mg and −3.9% with placebo.

  • semaglutide52 weeks

    STEP-HFpEF

    At 52 weeks, the KCCQ-CSS score improved by 16.6 points with semaglutide and 8.7 with placebo, and weight changed by −13.3% versus −2.6%.

  • semaglutide120 weeks

    STEP 1 (extension)

    From week 0 to week 68, weight fell by an average of 17.3% with semaglutide and 2.0% with placebo.

Sources

The original paper and the records consulted for this summary, with the date they were accessed.

  1. The Lancet Diabetes & Endocrinology.Lingvay I, et al. Once-weekly semaglutide 7·2 mg in adults with obesity and type 2 diabetes (STEP UP T2D): a randomised, controlled, phase 3b trial. Lancet Diabetes Endocrinol. 2025;13(11):935-948.accessed .
  2. National Library of Medicine (PubMed).PubMed record PMID 40961953 (abstract).accessed .
  3. The Lancet Diabetes & Endocrinology.Correction to Lancet Diabetes Endocrinol 2025; 13: 935-48. Lancet Diabetes Endocrinol. 2026;14(6):e9.accessed .
  4. ClinicalTrials.gov (National Library of Medicine).ClinicalTrials.gov record NCT05649137 (registration and primary outcomes).accessed .