Semaglutide Shows Sustained Weight Loss Over 4 Years


Added data from the SELECT trial helps to increase confidence in safety and efficacy of semaglutide, a glucagon-like peptide 1 medication.

The SELECT trial (NCT03574597) showed that weight loss with semaglutide (Wegovy; Novo Nordisk) was sustained over 4 years, doubling the longest follow up data of 2 years, according to Donna Ryan, MD, professor emeritus at the Pennington Biomedical Research Center, in an interview with Pharmacy Times.1 Ryan added that these data increase confidence in both the safety and efficacy of semaglutide for patients.

human heart and cardiogram on futuristic blue background for cardiovascular disease image | Image Credit: Artem -

Image Credit: Artem -

In the primary paper, which was previously published in the New England Journal of Medicine, findings showed there was a 20% reduction in major adverse cardiac events (MACE) for adults who had a body mass index (BMI) greater than 27 and pre-existing cardiovascular disease (CVD), although patients included did not have diabetes, according to Ryan.

“The more recent paper looks at the weight change in this population. What is important is that it confirms 4-year weight loss in all subgroups (men and women, all races, old and young, with and without pre-diabetes, all baseline BMI classes),” Ryan said in the interview. “More than 55% of semaglutide patients no longer qualified as having obesity [BMI 30+]. The dataset adds significantly to the semaglutide evidence--the population had 75% men and most weight loss studies are predominantly in women.”

The data from the initial SELECT trial could be used to evaluate the weight loss efficacy of semaglutide across subgroups, including race and geography, when compared to the placebo over 208 weeks. There were 17,604 individuals enrolled in the SELECT trial from 41 countries between October 2018 and March 2021, according to the study authors.1 Ryan added that there were no weight loss instructions, and patients received the standard of care for their respective cardiovascular risk, including smoking cessation, management of lipids, blood pressure, coagulation, and healthy lifestyle. Weight loss counseling was not given to patients. Further, an adjudicated committee verified all stroke, myocardial infarction, and cardiovascular deaths were monitored in the trial.

The results showed that weight loss of 5% or more, 10% or more, 15% or more, 20% or more, and 25% or more was achieved by 67.8%, 44.2%, 22.9%, 11%, and 4.9%, respectively, when compared to the placebo at 21.3%, 6.9%, 1.7%, 0.6%, and 0.1%, respectively. Additionally, approximately 52.4% of patients who received semaglutide had improvements in BMI compared to 15.7% in the placebo group at week 104. Approximately 12% achieved a BMI of less than 25 kg/m compared with only 1.2% with the placebo. Furthermore, 71% of patients at baseline were considered obese in the semaglutide group, which decreased to 43.3%, compared to 71.9% and 67.9%, respectively, in the placebo group.1

Compared to other weight loss medications, Ryan said that semaglutide achieved “somewhat less” weight loss, but she thinks that this can be explained because of patients not trying to lose weight. She added that investigators did not push drug doses, and instead they allowed dose reduction and treatment pauses. Ryan also noted that the data from the study are significant because of the number of older patients, males, and individuals from diverse countries included in the study.

Key Takeaways

  1. The SELECT trial showed sustained weight loss with semaglutide for up to 4 years, doubling the previously available data. This strengthens the evidence for semaglutide's efficacy in weight management.
  2. Patients received no specific weight loss instructions, suggesting semaglutide can be effective even without intensive lifestyle changes.
  3. A follow-up study, SELECT Life, will monitor patients from the SELECT trial to gather further data on the long-term effects of semaglutide use.

Discontinuation due to adverse events (AEs) occurred in 16.6% of those in the semaglutide group and 8.2% in the placebo group. Approximately 33.4% and 36.4% in the semaglutide arm and placebo arm, respectively, reported serious AEs (SAEs). Semaglutide was associated with lower SAEs that are driven by CVD or infections, according to the study authors.1

“There was no effect of BMI class on SAEs,” Ryan said. “Individuals with lower BMI classes did have higher rates of drug discontinuation, probably due to increased drug exposure and more [gastrointestinal] side effects.”

The investigators will initiate the SELECT Life trial, which will follow patients from the SELECT trial who enroll in the long-term, according to Ryan. SELECT Life will be an observational study using a survey method, Ryan explained.


Ryan DH, Lingvay I, Deanfield J, et al. Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial. Nat Med. May 13, 2024. doi:10.1038/s41591-024-02996-7

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