Research

STEP trials overview: semaglutide body-composition findings (2026 summary)

What the STEP trial program actually established about semaglutide for weight management, with a focus on the body-composition substudy findings most relevant to nutritional planning.

The STEP (Semaglutide Treatment Effect in People with obesity) trial program established the efficacy of subcutaneous semaglutide 2.4 mg weekly for chronic weight management. This article summarizes the major STEP trials with a focus on the body-composition findings most relevant to nutritional planning.

STEP-1 (Wilding et al., NEJM 2021)

STEP-1 randomized 1,961 adults with overweight or obesity (without Type 2 diabetes) to semaglutide 2.4 mg weekly versus placebo, both with lifestyle intervention, over 68 weeks. Mean weight loss in the semaglutide group was approximately 14.9% versus 2.4% in the placebo group.

Body-composition substudy: a subset of participants underwent DXA at baseline and at week 68. Total body weight loss was distributed approximately as fat mass and lean mass in proportions consistent with non-pharmacologic rapid weight loss; the proportion of total weight loss attributable to lean tissue in published analyses clusters around 35-40% in this trial cohort, with substantial individual variability.

STEP-2 (Davies et al., The Lancet 2021)

STEP-2 examined semaglutide 2.4 mg weekly versus 1.0 mg weekly versus placebo in adults with overweight or obesity and Type 2 diabetes over 68 weeks. The 2.4 mg group achieved approximately 9.6% mean weight loss versus 3.4% in the placebo group; the smaller magnitude in the T2D population is consistent with broader observations that GLP-1 weight loss is somewhat smaller in T2D versus non-T2D populations at the same dose.

STEP-3 (Wadden et al., JAMA 2021)

STEP-3 examined semaglutide 2.4 mg weekly with intensive behavioral therapy (IBT) versus placebo with IBT, in 611 adults with overweight or obesity. The semaglutide-plus-IBT group achieved approximately 16.0% mean weight loss versus 5.7% in the placebo-plus-IBT group. The trial provides evidence that adding semaglutide to a structured lifestyle intervention produces additive effects.

STEP-5 (Garvey et al., 2022)

STEP-5 examined semaglutide 2.4 mg over 104 weeks (longer duration than STEP-1’s 68 weeks). Mean weight loss was sustained at approximately 15-16% at 104 weeks. The longer-duration findings inform the discussion of continuation versus discontinuation of GLP-1 therapy.

STEP-8 (Rubino et al., JAMA 2022)

STEP-8 was a head-to-head comparison of semaglutide 2.4 mg weekly versus liraglutide 3.0 mg daily, with placebo control. The semaglutide group achieved approximately 15.8% mean weight loss versus 6.4% in the liraglutide group. STEP-8 is the most-cited evidence for the difference in weight-loss magnitude between the two semaglutide and liraglutide regimens.

Body-composition findings across STEP

Across the STEP trial body-composition substudies, several recurring observations:

• Total weight loss is composed of both fat-mass and lean-mass loss.
• The proportion of total weight loss attributable to lean tissue clusters in the approximately 25-40% range in the published analyses, with substantial individual variability.
• The proportion is broadly consistent with what is observed in non-pharmacologic rapid weight loss interventions of similar magnitude.
• Patients engaged in resistance-training and adequate-protein-intake interventions during weight loss generally show smaller proportional lean-mass loss in the supportive evidence base, though randomized data on resistance-training overlay specifically in GLP-1 trials are still emerging.

What the STEP findings inform for nutritional practice

The body-composition findings from STEP underpin the protein-and-resistance-training framework on this site. Specifically:

• The starting protein-target range (1.2-1.6 g/kg LBM/day for adults under hypocaloric conditions; 1.4-1.8 for older adults) is grounded in the broader hypocaloric-state protein literature with the body-composition findings from STEP and similar trials providing the rationale for emphasizing protein adequacy in this specific context.
• Resistance training as the second consistently-cited modifiable input is grounded in both general hypocaloric-state literature (Sardeli et al. 2018 meta-analysis) and the body-composition findings from STEP.

What STEP does not address

Several questions the STEP trials do not directly answer:

• Long-term (multi-year) lean-mass-loss trajectory.
• Functional consequences (strength, function) of lean-mass loss in the broader treated population beyond trial cohorts.
• Differential effect of various protein-target levels and resistance-training prescriptions specifically in GLP-1 patients (vs general hypocaloric-state populations).

These remain active areas of clinical research.

References

1. Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. New England Journal of Medicine. 2021;384(11):989-1002. (STEP-1.)
2. Davies M, Færch L, Jeppesen OK, et al. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2). The Lancet. 2021;397(10278):971-984.
3. Wadden TA, Bailey TS, Billings LK, et al. Effect of subcutaneous semaglutide vs placebo as an adjunct to intensive behavioral therapy on body weight (STEP 3). JAMA. 2021;325(14):1403-1413.
4. Garvey WT, Batterham RL, Bhatta M, et al. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nature Medicine. 2022;28(10):2083-2091.
5. Rubino DM, Greenway FL, Khalid U, et al. Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: the STEP 8 randomized clinical trial. JAMA. 2022;327(2):138-150.
6. Holmstrup ME, Fairman CM, Calanna S, et al. Body composition during pharmacologic weight loss with GLP-1 receptor agonists. Obesity Reviews. 2025;26(4):e13721.