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Semaglutide 2.4 mg: Weight Loss in Real-world Study Matches STEP Trial Program Findings


Semaglutide 2.4 mg (Wegovy, Novo Nordisk) was associated with a mean weight loss of 5.9% after 3 months among 150 patients treated for weight management at a referral center, according to findings of a new real-world study.

Investigators reported further that reduction in bodyweight with the glucagon-like peptide-1 receptor agonist increased to 10.9% at 6 months. Moreover, the Mayo Clinic team found that >50% of semaglutide users achieved weight loss of ≥10% at 6 months.

The findings are from the first retrospective study of the once weekly subcutaneous antiobesity medication since its approval in June 2021. The authors, led by Andres Acosta, MD, PhD, assistant professor of medicine, Mayo Clinic College of Medicine and Science, write “These results may support the applicability of semaglutide in a less controlled environment, as previously proven in RCTs.”

US Food and Drug Administration (FDA) approval of semaglutide for long-term weight management was the first such approval since 2014 and was based on the STEP clinical trial program. The series of large randomized controlled trials demonstrated a mean weight loss of 6% of body weight at 3 months and 12% of body weight at 28 weeks among semaglutide-treated participants with overweight or obesity.

The Mayo Clinic team found that >50% of semaglutide users achieved weight loss of ≥10% at 6 months.

To evaluate the weight loss outcomes with semaglutide in real-world clinical use, Acosta and colleagues performed a retrospective review of electronic medical record data from individuals in the Mayo Clinic Health system treated with 1.7 mg or 2.4 mg semaglutide between January 1, 2021, and March 15, 2022. For study inclusion, participants were required to have a body mass index (BMI) of ≥27 kg/m2 and be prescribed weekly semaglutide for ≥3 months. Major exclusion criteria included a history of bariatric procedures, receipt of other antiobesity medications, and being pregnant or having an active malignant neoplasm.

Percentage of weight loss at 3 months and 6 months was the researchers’ primary endpoint of interest. Secondary endpoints included the proportion of patients achieving weight loss of ≥5%, ≥10%, ≥15%, and ≥20% at the 2 specified times. The team performed a post hoc analysis of patients with or without type 2 diabetes (T2D) and of participants receiving different doses of semaglutide.

The final cohort numbered 175 participants with a mean age of 49.3 years. The majority were women (75.4%) and White (88.0%). Mean BMI was 41.3 kg/m2; 16.0% had type 2 diabetes, and 58.3% had 6-month follow-up data available.


Acosta et al found the mean weight loss at 3 months was 6.7 kg, which was equivalent to a mean weight loss of 5.9% (P <.001 from baseline). At 6 months, they report, mean weight loss was 12.3 kg, which was equivalent to a mean weight loss of 10.9% (SD, 5.8%) (P <.001).

Weight loss among the 102 participants with ≥6 months of follow-up data was:

  • ≥5% 87.3%
  • ≥10% 54.9%
  • ≥15% 23.5%
  • ≥20% 7.8%

Results of post-hoc analyses found that participants with T2D vs those without lost a lower mean percentage of bodyweight at 3 months (3.9% vs 6.3%) and at 6 months (7.2% vs 11.8%) (P=.005), a finding the authors note has been observed in other studies comparing weight loss among participants with and without T2D.

The majority of adverse events reported were gastrointestinal in nature and are a known class effect. The investigators do note several study limitations including the observational design which cannot control for potential confounding variables, the predominantly White cohort more than half of which were women, and data retrieval from the EMR database which may have increased potential for coding errors.

Acosta et al conclude, however, that overall “The findings of this cohort study suggest that semaglutide is clinically effective for weight loss at 3 and 6 months for people with overweight or obesity. Although our study lacked the stringent and closely controlled nature of RCTs, we report similar weight loss results within the same time period as in RCTs. Studies with greater sample sizes and longer periods of follow-up are further needed to support the effectiveness of semaglutide.”

Reference: Ghusn W, De la Rosa A, Sacoto D, et al. Weight loss outcomes associated with semaglutide treatment for patients with overweight or obesity. JAMA Network Open. 2022:5(9):e2231982. doi:10.1001/jamanetworkopen.2022.31982

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