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Semaglutide 2.4 mg Reduces Visceral Adiposity, Improves Lean Body Mass-to-Fat Mass Ratio


ENDO 2021

ENDO 2021: Obese individuals treated with semaglutide 2.4 mg vs placebo demonstrated improvements in body composition paralleling weight loss that may reduce risk for cardiometabolic disease.

In adults with overweight/obesity the glucagon-like peptide-1 receptor analogue semaglutide dosed once weekly at 2.4 mg was associated with reduced total fat mass and regional visceral fat mass as well as with an increase in proportion of lean body mass.

These findings, based on an analysis of the STEP 1 Study clinical trial, were presented virtually at ENDO 2021, the Endocrine Society's annual meeting, March 20-23, 2021.

Visceral adiposity is associated with major causes of death and disability, including heart attack, stroke, diabetes, hypertension, and fatty liver disease, as noted in a press release from The Endocrine Society, and its reduction is associated with reduced risk.

The randomized controlled STEP 1 clinical trial studied the effect of subcutaneous semaglutide 2.4 mg vs placebo on weight loss in 1961 adults aged ≥18 years with body mass index (BMI) ≥27 kg/m2 and ≥1 weight related comorbidity or BMI ≥30 kg/m2, without diabetes. Both groups received lifestyle intervention and the study ran for 68 weeks. Total fat mass, total lean body mass and regional visceral fat mass were measured using dual-energy absorptiometry (DEXA) at screening and week 68.

The current analysis included 140 patients (semaglutide n=95; placebo n=45); 76% were women; mean weight, 98.4 kg; BMI, 34.8 kg/m2. Baseline body composition was similar in those receiving semaglutide and placebo (see Sidebar).

For semaglutide vs placebo:

Total fat mass proportion:
43.4% vs 44.6%

Regional visceral fat mass proportion:
33.8% vs 36.3%

Total lean body mass proportion:
53.9% vs 52.7%


Percentage change in body weight from baseline to week 68 was -15.0% with semaglutide vs -3.6% with placebo.

In semaglutide-treated patients, reductions from baseline in total fat mass (-19.3%) and regional visceral fat mass (-27.4%) led to 3.5%-point reduction in proportion of total fat mass and a 2.0%-point reduction in proportion of visceral fat mass.

Although total lean body mass decreased from baseline (-9.7%) in the semaglutide group, it increased by 3 points relative to total body mass.

As weight loss increased from baseline to week 68, there was parallel improvement in the lean body mass:fat ratio. Overall, the ratio increased from baseline (1.34 [95% CI: 1.22,1.47]) to week 68 by 0.23 [0.14, 0.32]; improvement was greater in those with weight loss of ≥15% (n=44; 0.41 [0.28, 0.53]) vs weight loss of <15% (n=39; 0.03 [-0.05, 0.12]) (observed, dichotomized data; no imputation for missing data).

There were no major changes in body composition with placebo from baseline to week 68.

Findings from the STEP 1 trial were published in the New England Journal of Medicine in February 2021. Patients randomized to semaglutide 2.4 mg lost, on average, 15% of their baseline bodyweight vs weight loss of 2.4% in the placebo group. More than one-third of participants receiving semaglutide lost >20% of their weight. Many patients experienced improvements in risk factors for heart disease, blood sugar levels and quality of life.

Commenting on the current analysis in the Endocrine Society press release, lead researcher John Wilding, DM, FRCP, of the University of Liverpool in the Endocrine Society release said, “Our findings suggest that semaglutide, through body weight loss and improvement of body composition, has the potential to reduce the risk of heart disease, diabetes and stroke in people with overweight or obesity.”

Semaglutide injection 0.5 mg or 1 mg was approved in 2017 by the FDA as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus and in January 2020 to reduce cardiovascular risk in adults with type 2 diabetes and known heart disease.

Reference: Wilding J. Impact of semaglutide on body composition in adults with overweight or obesity: analysis of the STEP 1 study. Presented at ENDO 2021, March 20-23, 2021.

For more coverage of ENDO 2021, please click here.

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