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John Wilding, Rachel L. Batterham, Salvatore Calanna | New England Journal of Medicine | (2021)
Primary Link Pubmed DOI Openalex Full text (OA)

Abstract

Obesity is a global health challenge with few pharmacologic options. Whether adults with obesity can achieve weight loss with once-weekly semaglutide at a dose of 2.4 mg as an adjunct to lifestyle intervention has not been confirmed.

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Sample Definition And Size

Adults aged 18 or older with a BMI of 30 or greater, or a BMI of 27 or greater with weight-related coexisting conditions, who had previously attempted weight loss through diet. The study enrolled 1,950 participants across 129 sites in 16 countries. Participants were randomly assigned in a 2:1 ratio to receive semaglutide 2.4 mg weekly or placebo, in addition to lifestyle intervention. The trial was conducted over a 68-week period, followed by a 7-week off-treatment period. Key exclusion criteria included diabetes, a glycated hemoglobin level of 6.5% or greater, a history of chronic pancreatitis, acute pancreatitis within 180 days before enrollment, previous surgical obesity treatment, and use of antiobesity medication within 90 days before enrollment.

Study Type

Randomized, double-blind, placebo-controlled trial

Conflicts Of Interest

The study was sponsored by Novo Nordisk, the manufacturer of semaglutide. All authors had full access to study data, participated in drafting the manuscript, approved its submission for publication, and vouch for the accuracy and completeness of the data and for the fidelity of the trial to the protocol. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

Results Summary

The study found that semaglutide 2.4 mg weekly, combined with lifestyle intervention, led to a significant reduction in body weight compared to placebo. The estimated mean percentage change in body weight from baseline to week 68 was -14.9% with semaglutide and -2.4% with placebo (estimated difference, -12.5 percentage points; 95% confidence interval [CI], -14.0 to -11.0; P<0.001). Additionally, 86% of participants in the semaglutide group achieved at least a 5% reduction in body weight, compared to 31% in the placebo group (estimated odds ratio, 7.0; 95% CI, 5.6 to 8.7; P<0.001).

Referenced In

William Fan
a year ago
Nutrition

GLP-1 Agonists, Ozempic, and Weight Loss

Repost from my 91 day challenge

One major reason I started this challenge was to see whether I could lose weight at my age as or near as effective as people losing weight on GLP-1 Agonists like Ozempic, Wagovy, and Mounjaro. It felt like everywhere I looked, someone was trying these seemingly miracle cures and dropping a massive amount of weight, including people I knew personally.

I am generally apprehensive to try pharmaceuticals, especially ones that felt too new and too much of a miracle cure. But I read more about GLP-1 Agonists, I wanted to stay open minded about their value in the market and for health while also being clear eyed about the potential side effects.

As described in Glucagon-like peptide-1 receptor: mechanisms and advances in therapy, GLP-1 is a naturally occurring hormone in the body that is usually secreted in response to nutrient intake. This hormone does a number of things, but primarily triggers hunger satiety. Semaglutides like the brands described above mimic this hormone and largely drive weight loss through appetite suppression. Although the drugs were originally created for people with type II diabetes, trials on obese and overweight populations showed these drugs were wildly effective for those adults as well. This study saw a mean weight loss of -14.9% vs -2.4% against placebo in 68 weeks.

The impact of these drugs seem remarkable and anecdotally people say it truly reduces the "food noise" for them. Alongside of the weight loss are significant benefits in cardiovascular health, skeletal muscle-related diseases, obesity management, and neurodegenerative conditions as described by Zhikai Zheng et al. Though it's not clear to me how much of these additional benefits are equivalent to other means of weight loss or reversal of metabolic diseases.

So my last major question is about the risks of these drugs? This meta-analysis of 23 studies showed the:

The meta-analysis revealed that the adverse event associated with semaglutide is gastrointestinal in nature (nausea and vomiting). No significant differences were observed between semaglutide and comparator groups...Semaglutide appears to have a favorable safety profile across diverse patient populations and treatment durations, supporting its continued use in the management of type 2 diabetes mellitus and obesity

I remain cautious as this drug still needs long term studies before we can draw conclusions on its long term impacts especially for non-diabetic individuals. However, at this point it does seem these drugs are as "miracle drug" as I've seen.

Read Full Post
4
William Fan
a year ago
William Fan's 2025 91 Day Weight Loss Challenge

GLP-1 Agonists, Ozempic, and Weight Loss

One major reason I started this challenge was to see whether I could lose weight at my age as or near as effective as people losing weight on GLP-1 Agonists like Ozempic, Wagovy, and Mounjaro. It felt like everywhere I looked, someone was trying these seemingly miracle cures and dropping a massive amount of weight, including people I knew personally.

I am generally apprehensive to try pharmaceuticals, especially ones that felt too new and too much of a miracle cure. But I read more about GLP-1 Agonists, I wanted to stay open minded about their value in the market and for health while also being clear eyed about the potential side effects.

As described in 'Glucagon-like peptide-1 receptor: mechanisms and advances in therapy' , GLP-1 is a naturally occurring hormone in the body that is usually secreted in response to nutrient intake. This hormone does a number of things, but primarily triggers hunger satiety. Semaglutides like the brands described above mimic this hormone and largely drive weight loss through appetite suppression. Although the drugs were originally created for people with type II diabetes, trials on obese and overweight populations showed these drugs were wildly effective for those adults as well. This study saw a mean weight loss of -14.9% vs -2.4% against placebo in 68 weeks.

The impact of these drugs seem remarkable and anecdotally people say it truly reduces the "food noise" for them. Alongside of the weight loss are significant benefits in cardiovascular health, skeletal muscle-related diseases, obesity management, and neurodegenerative conditions as described by Zhikai Zheng et al. Though it's not clear to me how much of these additional benefits are equivalent to other means of weight loss or reversal of metabolic diseases.

So my last major question is about the risks of these drugs? This meta-analysis of 23 studies showed the:

The meta-analysis revealed that the adverse event associated with semaglutide is gastrointestinal in nature (nausea and vomiting). No significant differences were observed between semaglutide and comparator groups...Semaglutide appears to have a favorable safety profile across diverse patient populations and treatment durations, supporting its continued use in the management of type 2 diabetes mellitus and obesity

I remain cautious as this drug still needs long term studies before we can draw conclusions on its long term impacts especially for non-diabetic individuals. However, at this point it does seem these drugs are as "miracle drug" as I've seen.

Read Full Post
1