Weekly semaglutide injection associated with substantial weight loss in obesity
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Adults with obesity assigned the GLP-1 receptor agonist semaglutide experienced substantial weight loss compared with placebo, with more than half of participants losing 15% of body weight, according to data from the STEP 1 study.
“Semaglutide [Ozempic, Novo Nordisk] is the most impactful medication for the treatment of obesity, with 32% of participants losing at least 20% of their initial weight,” Robert Kushner, MD, professor of medicine and medical education at Northwestern University Feinberg School of Medicine, Chicago, told Healio. “It could be a game changer for those who struggle with obesity, which affects over 40% of American adults.”
For the Semaglutide Treatment Effect in People with Obesity (STEP) 1 trial, Kushner and colleagues analyzed data from 1,961 adults without diabetes with a BMI of at last 30 kg/m² or at least 27 kg/m² with a weight-related comorbid condition. Researchers randomly assigned participants in a 2:1 ratio to once-weekly subcutaneous semaglutide 2.4 mg or placebo for 68 weeks. Both groups received lifestyle intervention. Coprimary endpoints were percentage change in body weight and weight reduction of at least 5%. Researchers used the primary estimand to assess effects regardless of treatment discontinuation or rescue interventions.
Significant weight loss observed
Researchers found that mean change in body weight from baseline to week 68 was –14.9% for the semaglutide group and –2.4% for the placebo group, for an estimated treatment difference of –12.4 percentage points (95% CI, –13.4 to –11.5). Participants assigned semaglutide lost a mean –15.3 kg vs. –2.6 kg in the placebo group, for an estimated treatment difference of –12.7 kg (95% CI, –13.7 to –11.7).
Consistent with the GLP-1 receptor agonist class, nausea and diarrhea were the most common adverse events reported with semaglutide; these were typically transient and mild to moderate in severity, according to researchers. Within the cohort, 4.5% of participants in the semaglutide group and 0.8% of participants in the placebo group discontinued treatment due to gastrointestinal events.
Weight loss of at least 5% was significantly greater among participants in the semaglutide group at week 68 vs. placebo (86.4% vs. 31.5%), as was weight loss of 10% or more (69.1% vs. 12%) and weight loss of 15% or more (50.5% vs. 4.9%; P < .001 for all comparisons).
“We know that a lot of the health concerns we see in people who struggle with their weight, such as type 2 diabetes, hypertension, GERD and arthritis of the weight-bearing joints, are improved by losing at least 10% of body weight,” Kushner said. “In this study, nearly 70% of participants were able to achieve this 10% weight loss threshold by taking semaglutide.”
Kushner said future work must involve a more diverse patient population, including more men and people from underrepresented backgrounds.
“Other research questions include long-term use of the medication, how to use it effectively in primary care offices, and benefits in reducing cardiovascular disease,” Kushner said. “The SELECT trial is already underway.”
‘A long way to go’
In commentary accompanying the study, Julie R. Ingelfinger, MD, professor pediatrics at Harvard Medical School and senior consultant in pediatric nephrology at Massachusetts General Hospital for Children, and Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research at the Maine Medical Center Research Institute in Scarborough, called the data encouraging and “a good beginning,” but noted the trial excluded several populations, including men and Black and other nonwhite adults, raising questions about efficacy of semaglutide among those groups. Additionally, more than 40% of the cohort had prediabetes; questions remain about the efficacy of the drug for adults with obesity and normal glucose tolerance. The authors also wrote that subcutaneous administration may not be “palatable or cost-effective in the long run.”
“Similarly, given the effectiveness of bariatric surgery in regard to both weight loss and glucose tolerance, studies comparing these two distinct forms of therapy (surgery and pharmacologic therapy) will be required,” the researchers wrote. “In sum, we have a long way to go to control the obesity epidemic, but STEP 1 serves its name well.”
For more information:
Robert F. Kushner, MD, can be reached at rkushner@northwestern.edu; Twitter: @DrRobertKushner.
Perspective
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This is a long-awaited paper. The findings are notable because of the sheer magnitude of the weight loss, which is 14.9%. Even if you subtract the 2.4% weight loss in the placebo group, you still end up with over 12% weight loss for those assigned semaglutide. The difference compared against other available obesity drugs is basically doubled.
Additionally, with weight loss after undergoing sleeve gastrectomy typically around 25%, we are narrowing the gap between drugs and surgery for obesity treatment. The adverse effect profile of semaglutide is also very good, and this agent has the advantage of being a once-weekly drug.
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