Phase 3a Step 1 study investigating the use of Semaglutide (Novo Nordisk), a glucagon-like peptide-1 (GLP-1) agonist, some say it has been properly named for weight loss.
“In short, we have a long way to go to control obesity Epidemic … But on the surface, the STEP 1 exam (as its name suggests) is a good start, “writes Dr. Julie R. Ingelfinger, co-editor of Harvard Medical School in Boston, Massachusetts. .. New England Journal of Medicine, And Clifford J. Rosen, MD, School of Medicine, Tufts University, also in Boston.
Test results by John PH Wilding, DM, University of Liverpool, UK, and colleagues and accompanying editorials Published online February 10 New England Journal of Medicinee.
“The results are encouraging, and quite a few patients in the semaglutide group show clinically significant weight loss,” emphasizes Ingelfinger and Rosen.
However, they also said, “Despite the positive results of this study, there are some important limitations to this study.” “Mainly gastrointestinal-nausea-related adverse events (mainly gastrointestinal-nausea.” , Sometimes with vomiting, diarrhea). ” Agent. “
Two UK experts drew similar points and spoke to the UK Science Media Center.
“This is a well-designed study with clear discoveries,” said Dr. Baptist Lurent of the London School of Economics and Tropical Medicine, and Semaglutide “becomes a game changer in the fight against obesity.” It’s likely. “
However, if this drug is approved for this use at this dose, the patient should closely monitor gastrointestinal disorders, “what is happening after treatment is stopped, and shorter. You also need to better understand if you can take it for a period of time. “
Sir Stephen O’Reilly of the Cambridge University MRC Metabolic Diseases Unit points out: “GLP-1 is made by cells in the intestine, which raises blood levels after a meal and provides some of the signals to the brain. It turns out to be” full “, so a GLP-1 agonist. Has been studied as an appetite suppressant, in addition to its approved use for treatment. Type 2 diabetes..
Only about 4.5% of STEP 1 participants stopped taking semaglutide due to gastrointestinal problems, but more participants in that group reported gallstone problems that could follow rapid weight loss. He said he did.
“There is no evidence that semaglutide has an adverse effect of its nature, unlike some previous appetite suppressants that have caused serious psychological and psychiatric side effects,” O’Rahilly said. ..
In short, “This is the beginning of a new era of obesity treatment development, and the future direction is to achieve levels of weight loss comparable to semaglutide with few side effects.”
“”Imminent need“” To deal with obesity; semaglutide submitted for obesity
Ingelfinger and Rosen say there is an “urgent need” to address the global increase in coexistence associated with obesity and weight.
Sustained long-term weight loss from diet and exercise is difficult. Behavioral weight loss strategies “often fail” Obesity surgery They write that they are invasive and often follow a final weight recovery.
In addition, Wilding and colleagues said, “Use available [weight-loss] The drug remains limited by modest efficacy, safety concerns, and cost. “
Subcutaneous semaglutide approved for the treatment of type 2 diabetes Ozenpick) In adults at doses up to 1 mg / week, higher doses induced weight loss. The current study is a global study of the therapeutic effects of semaglutide in obese patients in four trials (STEP 1, 2, 3, and 4) aimed at testing the safety and efficacy of subcutaneous semaglutide 2.4 mg / week for weight loss. It is part of the program.
Top line result of step 1 Presented June 4, 2020.
And as Previously reported, STEP 3 Results — A 68-Week Study of Semaglutide and Placebo with 611 Participants Who Received Very Intensive Diet and Exercise Counseling — Presented at Virtual Obesity Week® 2020 conference.
Four trials of semaglutide for weight loss have been completed and the data have been submitted to the US Food and Drug Administration. December 4, 2020 (A decision is expected within 6 months) and to the European Medicines Agency December 18, 2020..
Most patients had a 5% weight loss with semaglutide
In the STEP 1 study, 1961 adults with a body mass index (BMI) of 30 kg / m or higher were enrolled.2 Or ≥ 27 kg / m2 There is at least one weight-related coexistence at 129 sites in 16 countries in Asia, Europe, North America and South America, but no type 2 diabetes.
The average age of participants was 47, and three-quarters were women.
Most participants were Caucasian (76%), followed by Asians (13%), Blacks or African Americans (6%), or others (5%).
On average, they had a BMI of 38 kg / m2 I weighed 105 kg. Three-quarters had one or more coexistence conditions.
Participants were randomized to receive semaglutide (1306 patients) or placebo (655 patients) added to the lifestyle intervention.
All received 17 individual counseling sessions each month, learned to adhere to a 500 calorie / day deficiency diet, were encouraged to walk 150 minutes each week, and recorded their daily diet and exercise (diary or exercise). Used app).
Semaglutide was given a prefilled pen injector at a dose of 0.25 mg / week for the first 4 weeks and increased to 2.4 mg / week by week 16 (less if the patient had unacceptable side effects).
At week 68, participants in the semaglutide vs. placebo group showed greater mean weight loss (14.9% vs. 2.4%, or 15.3 kg vs. 2.6 kg).
Participants in the semaglutide vs. placebo group were much more likely to have lost at least 5% (86% vs. 31.5%) of initial body weight or at least 10% (69.1% vs. 12.0%) of initial body weight, or at least 15. .. % Of initial weight (50.5% vs. 4.9%; P <.001) in all three comparisons.
Approximately 80% of participants adhered to the study treatment. One-third of the participants in the semaglutide group who completed the study lost at least 20% of their initial body weight. This is close to 20% to 30% of the weight loss reported 1-3 years after sleeve gastrectomy.
Participants in the semaglutide group also had significant improvements in hip circumference and levels A1c, C-reactive protein (marker of inflammation), and fasting Lipid, And SF-36 and IWQOL-Lite-CT questionnaire physical function scores.
Among them editorial, Ingelfinger and Rosen, “Daily Oral Semaglutide [already approved in 7-mg and 14-mg doses for the treatment of type 2 diabetes as Rybelsus] It may be more attractive to many as a weight loss drug than a weekly subcutaneous dose. Semaglutide is the first GLP-1 agonist available as an oral preparation.
Ongoing semaglutide effect on heart disease and heart disease stroke Overweight or obese patients (selectThe study (scheduled to be completed in 2023) will shed light on cardiovascular outcomes 2.5 to 5 years later.
With gastrointestinal disorders “”Important restrictions“”
Gastrointestinal disorders (usually nausea, usually nausea) in semaglutide participants than in the placebo group diarrhea, Vomiting, and constipation74.2% vs 47.9%), which was mostly transient and mild to moderate severity, but led to more discontinuation of treatment (7.0% vs 3.1%).
More patients in the semaglutide vs. placebo group had gallbladder-related disorders (2.6% vs 1.2%, predominantly cholelithiasis) and mild Acute pancreatitis (Participants 3-0), but there was no difference between the groups in the neoplasm.
Wilding et al. Recognized the limitations of the study, including enrolling predominantly female, predominantly non-white participants, relatively short, and excluding patients with type 2 diabetes.
Mean placebo-corrected weight loss with 2.4 mg / week subcutaneous semaglutide was greater than the once-daily subcutaneous dose of 3.0 mg. Liraglutide (((Saxender, Novo Nordisk) —The only GLP-1 agonist approved for weight management — in 56 weeks scale Trial (12.4% vs 4.5%); However, the populations of the two studies were different.
This study was supported by Novo Nordisk. The author’s disclosure is available in the article. Ingelfinger is Deputy Editor-in-Chief and Rosen is Deputy Editor-in-Chief of The New England Journal of Medicine. Ingelfinger, Rosen, and Leurent have not reported any relevant financial relationships. O’Rahilly is currently collaborating with Novo Nordisk scientists in unrelated fields and is a consultant to the company.
N Engl J Med.. Published online on February 10, 2021. paper, editorial
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