PLAINSBORO, NJ, March 23, 2021 / PRNewswire / – Recent results from the STEP phase 3a clinical trial program showed weight loss with a once-weekly 2.4 mg versus placebo dose treatment of subcutaneous semaglutide. In the STEP 4 trial, study participants who reached the maintenance dose of semaglutide 2.4 mg during a 20-week running period were randomized to continue treatment with semaglutide 2.4 mg or switch to placebo for 48 weeks.1 The full results of the STEP 4 test were presented today at the 2021 Annual Endocrine Society (ENDO) Annual Meeting and published in the Journal of the American Medical Association.
“For people with obesity, sustaining weight loss in the long term is challenging because both physiological and hormonal changes that come after initial weight loss can lead back to weight loss. called metabolic change, leading to higher levels of hunger and appetite while reducing energy expenditure, “said Dr. Domenica Rubino, chief examiner of the STEP 4 test and Director of the Washington Center for Weight Management and Research. “Like any other chronic disease, obesity requires an individual, individualized approach to care, including medication and lifestyle components.”
Two specific statistical methods for the 2.4 mg semaglutide effect assessment were used in the STEP 4 trial; a primary statistical approach (treatment policy estimate) that assessed treatment effects regardless of whether they adhered to or used other anti-obesity treatments, and a secondary statistical approach (outcome estimate). evaluated the effect of treatment if all participants in the trial adhered to the treatment at random and did not initiate any other treatment modalities.2
After the 20-week running period, patients treated with 2.4 mg semaglutide for an additional 48 weeks continued to lose weight with a statistically significant additional weight loss of 7.9% (8.8% for estimated outcome. ), and those switched to placebo after the 20-week running period back 6.9% of their body weight (6.5% for estimated test results) from week 20 to week 68. The difference estimated treatment [ETD] for treatment policy estimate was -14.8%; 95% confidence interval [CI]: -16.0, -13.5; p <0.0001.1 Seen as a secondary limit, semaglutide-treated 2.4 mg patients throughout the 68-week trial achieved a total weight loss of 17.4% (18.2% for test result estimation). Both treatment groups followed a low-calorie diet and an increased physical activity program throughout the study.1
“Obesity is a serious, harmful, and, unfortunately, misunderstanding that requires long-term care that may include medication,” he said. Anne Phillips, MD, senior vice president, Clinical, Medical and Regulatory Affairs at Novo Nordisk. “These data will help show how this new treatment could make a difference for people struggling to find options. With semaglutide 2.4 mg, we hope we can living with obesity to help achieve meaningful weight loss. “
The most common side effects with semaglutide 2.4 mg were nausea, diarrhea and stomach upset (mainly transient and moderate-to-severe). During the run, 5.3% of participants stopped their treatment due to adverse events. During the randomized period, 2.4% and 2.2% stopped treatment with 2.4 mg semaglutide and placebo, respectively.1
About STEP 4 and the STEP clinical trial program
STEP 4 was a placebo-controlled, double-blind, multicenter, placebo-controlled 3a phase 3 trial that compared the safety and efficacy of 2.4 mg subcutaneous semaglutide versus placebo-altered body weight. The trial was designed to evaluate the effect of sustained resistance to seizaglutide 2.4 mg in obese adults (BMI ≥30 kg / m2), or fat (BMI ≥27 kg / m2) with at least one weight-related comorbidity and without type 2 diabetes (HbA)1c <6.5%). In the 20-week running period (Week 0 to Week 20), participants were treated with semaglutide (16-week dose increase, and 4 weeks later at the target dose) in support of lifestyle intervention ( –500 kcal / day diet combined with 150 minutes / week of physical activity). After the run-down period, the 803 people who reached the maintenance dose of semaglutide (2.4 mg) reduced their average body weight from 107.2 kg (Week 0) to 96.1 kg (Week 20) and were randomized ( in a 2: 1 ratio) to continue treatment with semaglutide 2.4 mg or switch to placebo for another 48 weeks (Week 20 to Week 68).1,2
The main endpoint of the trial was the percentage change in body weight from randomization (Week 20) to the end of treatment (Week 68). Positive secondary endpoints included change in waist circumference, systolic blood pressure, and physical activity score on the 36-item Short Form Study (SF-36), randomly assessed ( Week 20) to the end of treatment (Week 68).3 Supportive secondary endpoints included a percentage change in body weight from baseline (Week 0) to the end of treatment (Week 68).3
STEP (S.emaglutide T.reatment E.ffect into P.eople with obesity) is a phase 3 clinical improvement program with once-weekly subcutaneous semaglutide 2.4 mg in obesity. The global phase 3a clinical program is made up of four trials and has enrolled approximately 4,500 adults with overweight or obesity.2
About 2.4 mg subcutaneous semaglutide for weight management
Semaglutide 2.4 mg once a week is being studied by Novo Nordisk as a potential treatment option for obesity. Semaglutide is an analogue of the human peptide-1 hormone (GLP-1) similar to glucagon.4
Obesity is a chronic, progressive and misunderstood disease that requires long-term medical management.5.6 One major misconception is that this is a degenerative power disorder, when there is a basic biology that prevents people from losing and keeping away weight.7 Obesity is affected by a number of factors, including genetics, desire signals, behavior and the environment.7 It is a gate disease and is associated with at least 60 other health conditions.8 The current COVID-19 epidemic has clarified that obesity also increases the risk for serious illness and hospitalization due to COVID-19.9,10,11,12
The global rise in the incidence of obesity is a public health issue that has huge cost implications for health care systems.13.14 In United States, more than 42% of adults live with obesity.15
1 Domenica R, Abrahamsson N, et al. Maintain weight loss with 2.4 mg semaglutide once a week in overweight or obese adults reaching a maintenance dose. Presented at the ENDO AGM. March 20-23, 2021.
2 Kushner RF, Calanna S, Davies M, et al. Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP 1 to 5 Tests. Obesity. 2020; 28: 1050-1061.
3 ClinicalTrials.gov. Research Study examining how well Semaglutide works in overweight or obese people (STEP 4). ClinicalTrials.gov Identifier: NCT03548987. Available from: https://clinicaltrials.gov/ct2/show/NCT03548987. Finally reached March 2021.
4 J Lau, P Bloch, L Schaffer, et al. Sequencing Analog Semaglutide Once a Week Similar to Glucagon-1 (GLP-1). J Med Chem. 2015; 58: 7370-80.
5 American Medical Association. AMA will adopt new policies on the second day of voting at the AGM. Obesity as a disease. Available at: https://news.cision.com/american-medical-association/r/ama-adopts-new-policies-on-second-day-of-voting-at-annual-meeting,c9430649. Last accessed: March 2021.
6 Bray GA, Kim KK, Wilding JPH. World Obesity Alliance. Obesity: a progressive relapsing disease process. Position statement of the World Obesity Federation. ObesRev. 2017; 18 (7): 715-723. doi: 10.1111 / obr.12551.
7 Wright SM, Aronne LJ. Causes of obesity. Abdominal image. 2012; 37 (5): 730-732.
8 Bays HE, McCarthy W, Christensen S, et al. Obesity algorithm, presented by the Society for the Treatment of Obesity. Available at: https://obesitymedicine.org/obesity-algorithm/. Last accessed: March 2021.
9 Finer N, Garnett SP and Bruun JM. COVID-19 and obesity. Clin Obes. 2020; 10: e12365.
10 Ryan DH, Ravussin E and Heymsfield S. COVID 19 and the obese patient – The editors speak out. Obesity (Silver Spring). 2020; 28: 847.
11 Body and risk index for COVID-19-related hospitalization, intensive care unit admission, aggressive mechanical ventilation, and death – United States, March-December 2020. Centers for Disease Control and Prevention. https://www.cdc.gov/mmwr/volumes/70/wr/mm7010e4.htm?s_cid=mm7010e4_w. Updated March 8, 2021. Last reached: March 2021.
12 Obesity, Race / Ethnicity, and COVID-19. Centers for Disease Control and Prevention. https://www.cdc.gov/obesity/data/obesity-and-covid-19.html. Updated March 9, 2021. Last reached: March 2021.
13 World Health Organization. Obesity information sheet or. 311. Available at: http://www.who.int/mediacentre/factsheets/fs311/en/. Last accessed: March 2021.
14 Cawley J, Meyerhoefer C, Biener A., et al. Savings in medical costs are associated with a reduction in body mass index among obese U.S. adults, depending on diabetes status. Pharmacoeconomics. 2015; 33: 707–722
15 Information on adult obesity. Centers for Disease Control and Prevention. https://www.cdc.gov/obesity/data/adult.html. Updated February 11, 2020. Last accessed: March 2021.
SOURCE Novo Nordisk