University of Copenhagen

Nearly seven years after the FDA approved Novo Nordisk’s Ozempic for diabetes treatment, this medication and other GLP-1 receptor agonists have proven very effective in promoting weight loss. For the millions struggling with obesity, they offer a way to reduce appetite, manage blood sugar levels, lose weight, and decrease the risk of the comorbidities associated with having a higher body mass. The World Obesity Federation has warned that by 2035 approximately 4.4 billion people globally will be classified as obese. This would lead to a predicted $4.32 trillion burden on global economies and consequences for healthcare systems comparable to the impact of Covid-19 in 2020. Studies have shown that GLP-1 drugs can help individuals achieve an average weight loss of 15% of their total body weight. In terms of immediacy and relative ease, this far outperforms the rate of weight loss that can be achieved with lifestyle interventions and approaches the results from surgical treatments. presented by Health Tech What’s Keeping Healthcare CIOs Up at Night: How to Improve Patient Satisfaction by Handling Calls More Efficiently Health systems have spent billions on portals while investments in modernizing the voice channel — the dominant preference of healthcare consumers — have taken a backseat. By Stephanie Baum Despite promising outcomes, the question remains: do medications like Novo Nordisk’s Wegovy, Eli Lilly’s Mounjaro, Ozempic, and the 120 other treatments currently in development provide a sustainable, long-term solution for obesity? Weight loss alone does not guarantee improved health outcomes, especially for the long-term. On the contrary, reduced weight loss can be detrimental to health if a significant portion of that lost weight is accounted for by muscle mass. Furthermore, when patients discontinue the medication, they could regain weight, mainly in the form of fat. These concerns were raised in multiple studies, such as the STEP 1 and STEP 4 trials, which reported significant weight regain after discontinuation of the semaglutide treatment. This could become a vicious cycle leading to sarcopenia, frailty and long-term health issues. Both medical professionals and the media are increasingly educating patients about the potential downsides of these medications, emphasizing that they are not a ‘solve-all’ solution. As multi-billion investment continues to pour into the R&D of future obesity medications, the need for evidence generation of health benefits beyond short-term weight loss will be critical to the decision-making of healthcare providers and payers. It is time to set a new standard for evidence generation in obesity clinical trials. Next, we discuss why objective assessments of physical activity should be an integral component of obesity trials. Physical activity, a key aspect of lifestyle intervention, is commonly included in clinical trials in obesity. For example, in the STEP 4 clinical trial of semaglutide, participants in both the treatment and placebo groups were instructed to increase their physical activity by 150 minutes weekly. As such, approved GLP-1 medications are labelled as adjunct treatments to a lifestyle intervention including increased physical activity. More importantly, increased physical activity or exercise is critical to long-term health benefit. The University of Copenhagen led a comprehensive study to examine the interactions between GLP-1 medication and physical activity using a multi-armed randomised control trial. They demonstrated that the combination of GLP-1 medication and physical activity produced more sustainable impact on obesity management than the use of GLP-1 medication alone. Sponsored Post The Future of Hospitals and Pharma Companies Will Depend on Strength of Healthcare Analytics Insights PurpleLab® stands out from others in this sector by providing its data analytics services to several different groups of users across healthcare and pharma companies. By Stephanie Baum Therefore, the adherence to a physical activity intervention among participants likely has a substantial impact on the efficacy of the treatment, especially on muscle preservation and long-term maintenance. Drug developers will need to supply more robust data to reassure payers and healthcare professionals of the long-term sustainability of medication-aided weight loss. This will be what distinguishes the most effective treatments as the industry advances obesity care. Accounting for this variable in a clinical trial can reduce statistical noise in the data, which is critical to obtaining a more comprehensive and nuanced picture of the treatment effect. So far, physical activity has been self-reported via paper diaries or apps, and no objective data collected to quantify participants’ physical activity levels. While traditional self-reported methods provide some insights, they are subjective and susceptible to recall bias. On the other hand, wearable technology has been widely used by academic researchers and consumers to objectively track physical activity, such as step count, speed, and duration, delivering a more accurate view than self-reported data. Wearables can also provide objective measures of sleep, which is negatively impacted by obesity and at the same time could interfere with obesity intervention. Incorporating these objective digital measures into clinical trials will give a clearer picture of how pharmacotherapy and lifestyle factors influence a patient’s weight loss, muscle mass, and long-term maintenance, and better support drug developers with more precise and robust evidence on the efficacy of their novel therapies. Beyond the use of wearable technology to track lifestyle factors during intervention, it also provides novel outcome assessments as meaningful clinical endpoints needed for regulatory approval and payer reimbursements. Wearable technology can objectively assess the quality of physical activity and level of physical fitness. It is well established in the literature that speed and amount of walking improve with muscle strength, physical capacity, and cardiovascular fitness, and can predict long-term health outcomes. With wearable technology, we can now assess walking speed and bouts in the real world with minimal patient burden. In addition to quantifying activity, newer technology such as optical photoplethysmogram (PPG) on wearables has the potential to estimate VO2Max and sleep apnea. These real-world insights can reveal how obesity treatments impact daily functioning and quality of life. Not only do wearable-derived digital measures provide more meaningful clinical endpoints than weight loss for clinical trials, but they can also inform personalized and effective treatment plans​​ in the real world. There is a need to set standards against the levels of physical activity required to maximize the efficacy of GLP-1 medications. Incorporating wearable DHTs into obesity trials and routine care can help develop evidence-based guidelines. By understanding the optimal types and amounts of physical activity that support muscle preservation and weight maintenance and incorporating these into clinical research, healthcare providers can offer more targeted and practical recommendations to patients, which may help them to shift the pounds for the long term.

Results from 68-week study of 407 adults with obesity and moderate knee osteoarthritis showed semaglutide 2.4 mg significantly reduced body weight, knee osteoarthritis-related pain, and improved physical function1 Obesity is a major risk factor of knee osteoarthritis development and disease progression2-4 Semaglutide is not approved in the U.S. for the treatment of knee osteoarthritis PLAINSBORO, N.J., Oct. 30, 2024 /PRNewswire/ -- Today, The New England Journal of Medicine published results from Novo Nordisk's STEP 9 phase 3 clinical trial that studied semaglutide 2.4 mg compared to placebo as an adjunct to lifestyle modifications in reducing body weight and knee osteoarthritis-related pain in adults with obesity, and a clinical and radiologic diagnosis of moderate knee osteoarthritis, and pain that is at least moderately severe.1 According to the published trial, semaglutide met the study's primary endpoints and was superior to placebo in significantly reducing body weight and knee osteoarthritis-related pain, as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. In addition, the trial met a key confirmatory secondary endpoint of improving patients' physical function.1 In patients with a mean baseline body weight of 239.5 pounds, semaglutide led to a –13.7% mean change from baseline in body weight at week 68 versus –3.2% with placebo ([95% confidence interval (CI) –12.3, –8.6]; P<0.001). Semaglutide also led to a mean change from baseline (70.9) in the WOMAC pain score of –41.7 at week 68 versus –27.5 with placebo ([95% CI –20.0, –8.3]; P<0.001). WOMAC is a 24-item patient-reported questionnaire that assesses clinically important symptoms of pain, stiffness, and physical function in patients with hip and/or knee osteoarthritis (OA).1,5 A greater improvement in physical functioning scores was also observed from baseline at week 68 among trial participants taking semaglutide versus placebo (mean change: 12.0 versus 6.5 points [95% CI 3.1, 8.0], P<0.001]) as measured by the 36-Item Short Form Survey (SF-36v2).1 Obesity is considered a major risk factor for the development and progression of knee osteoarthritis, a common type of osteoarthritis that can lead to chronic pain and reduced mobility.2-4 Obesity contributes to the development of knee osteoarthritis through increased mechanical stress on weight-bearing joints, metabolic factors, and obesity-related inflammation.2,3 "Obesity-related knee osteoarthritis is a progressive condition that can lead to pain and stiffness of the knee and impair critical daily functions such as walking or moving around. The risk of developing the condition is more than four times higher in people with obesity. Weight reduction along with physical activity is often a recommended approach to managing painful symptoms, but adherence can be challenging," said lead study author Henning Bliddal, MD, M.Sci., The Parker Institute, Copenhagen University Hospital, Denmark. "There is a significant need for non-surgical and sustainable treatment options for those living with obesity-related osteoarthritis. The STEP 9 trial aimed to provide rigorous evidence as to how semaglutide may help these people." The study implemented a targeted approach to safety data collection, with investigators recording only serious adverse events (SAEs), adverse events (AEs) leading to treatment discontinuation, AEs requiring invasive knee procedures, medication error, acute pancreatitis, COVID-19, and pregnancy or pregnancy-related AEs.1 AEs leading to treatment discontinuation occurred in 6.7% of patients in the semaglutide group and 3.0% of patients in the placebo group. The most common AEs leading to treatment discontinuation were gastrointestinal disorders (2.2% of patients in the semaglutide group and 0% of patients in the placebo group) and neoplasms (benign, malignant, and unspecified) (semaglutide, 1.9%; placebo, 1.5%). The incidence of SAEs was similar in both groups (semaglutide, 10.0%; placebo, 8.1%).1 STEP 9 was a randomized, double-blind, placebo-controlled multicenter trial of 407 adults aged ≥18 years with obesity (BMI ≥30 kg/m2) and a clinical diagnosis of knee osteoarthritis per American College of Rheumatology criteria with moderate radiographic changes (Kellgren–Lawrence grade 2 or 3) in the target knee. Participants also had pain due to knee osteoarthritis, with a WOMAC pain score ≥40 out of 100 at randomization.1 "Obesity is a complex metabolic disease associated with multiple co-morbid conditions, including knee osteoarthritis," said Anna Windle, PhD, Senior Vice President, Clinical Development, Medical and Regulatory Affairs, Novo Nordisk. "The STEP 9 results are encouraging and provide important information about the effect of semaglutide, a glucagon-like peptide-1 receptor agonist, on knee osteoarthritis outcomes in people with obesity. We look forward to working with regulatory authorities on next steps based on these findings." About obesity Obesity is a serious chronic, progressive, and misunderstood disease that requires long-term management.6-8 One key misunderstanding is that this is a disease of just lack of willpower, when in fact there is underlying biology that may impede people with obesity from losing weight and keeping it off.6,7 Obesity is influenced by a variety of factors, including genetics, social determinants of health, and the environment.9 The prevalence of overweight and obesity is a public health issue that has severe cost implications to healthcare systems.10,11 In the U.S., about 40% of adults live with obesity.12 About the STEP 9 trial (semaglutide 2.4 mg) STEP 9 was a randomized, double-blind, placebo-controlled multicenter trial designed to evaluate the efficacy of semaglutide 2.4 mg versus placebo as an adjunct to lifestyle modifications (counseling on a reduced-calorie diet and physical activity) in reducing body weight and knee osteoarthritis-related pain in patients with obesity and a clinical and radiologic diagnosis of moderate knee osteoarthritis, and pain that is at least moderately severe.1 Participants were randomized 2:1 to receive once-weekly subcutaneous semaglutide 2.4 mg or placebo for 68 weeks, followed by 7 weeks' off-treatment follow-up. There was a 16-week dose escalation to allow for adjustment to therapy (gastrointestinal adverse reactions). The study randomized participants between October 2021 and March 2022.1 All endpoints were measured from baseline to week 68. The primary endpoints were the percentage change in body weight and change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score.1 The trial enrolled 407 adults and was conducted in 11 countries at 61 investigator sites.1 Semaglutide is not approved for the treatment of knee osteoarthritis. Safety and efficacy are not established, and there is no guarantee that semaglutide will become commercially available for this use under clinical investigation. About Novo Nordisk Novo Nordisk is a leading global healthcare company that's been making innovative medicines to help people with diabetes lead longer, healthier lives for more than 100 years. This heritage has given us experience and capabilities that also enable us to drive change to help people defeat other serious chronic diseases such as obesity, rare blood, and endocrine disorders. We remain steadfast in our conviction that the formula for lasting success is to stay focused, think long-term, and do business in a financially, socially, and environmentally responsible way. With U.S. headquarters in New Jersey and commercial, production, and research facilities in seven states plus Washington DC, Novo Nordisk employs approximately 8,000 people throughout the country. For more information, visit novonordisk-us.com, Facebook, Instagram, X, LinkedIn, and YouTube. References Bliddal H, Bays H, Czernichow S, et al. Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis. N Engl J Med. 2024; 391:1573-83. Centers for Disease Control and Prevention. Arthritis risk factors. Last accessed: September 2024. Available at . World Health Organization. Osteoarthritis. Last accessed: October 2024. Available at: . Nedunchezhiyan U, Varughese I, Sun AR, et al. Obesity, inflammation, and immune system in osteoarthritis. Front Immunol. 2022;13:907750. doi:10.3389/fimmu.2022.907750. ClinicalTrials.gov. Research study looking at how well semaglutide works in people suffering from obesity and knee osteoarthritis. Last accessed: October 2024. Available at: . Kaplan LM, Golden A, Jinnett K, et al. Perceptions of barriers to effective obesity care: results from the national action study. Obesity. 2018;26(1):61-69. Bray GA, Kim KK, Wilding JPH; World Obesity Federation. Obesity: a chronic relapsing progressive disease process. A position statement of the World Obesity Federation. Obes Rev. 2017;18(7):715-723. Garvey WT, Mechanick JI, Brett EM, et al. American association of clinical endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract. 2016;22 (Suppl 3):1-203. Centers for Disease Control and Prevention. Causes of obesity. Last accessed: October 2024. Available at: . World Obesity Federation. World Obesity Atlas 2023. Last accessed: October 2024. Available at: . Centers for Disease Control and Prevention. Why it matters. Last accessed: October 2024. Available at: . Centers for Disease Control and Prevention. Obesity and Severe Obesity Prevalence in Adults: United States, August 2021–August 2023. Last accessed October 2024. Available at: . © 2024 Novo Nordisk All rights reserved. US24SEMO01198 October 2024 SOURCE NOVO NORDISK INC. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Antag Therapeutics has announced that the FDA has accepted the investigational new drug (IND) application for its lead drug candidate, AT-7687. This will enable Antag Therapeutics to initiate a phase 1 clinical trial to evaluate the small molecule drug candidate in both healthy lean and healthy obese individuals. The study will also explore the combination of AT-7687 and semaglutide, the active compound of weight management drugs Ozempic and Wegovy. “We are thrilled to receive the FDA’s acceptance of our IND application for AT-7687,” said Alexander Sparre-Ulrich, Founder and CEO of Antag Therapeutics. “This marks a major step forward in advancing our clinical development program and brings us closer to providing a potential new treatment for patients with obesity and cardiometabolic diseases. We are excited to begin our phase I study and further demonstrate the therapeutic potential of AT-7687 and GIPR antagonism.” Based in Copenhagen, Denmark, Antag Therapeutics is a biopharmaceutical company developing treatments for obesity and cardiovascular disease that target the glucose-dependent insulinotropic polypeptide (GIP) receptor. The company’s first-in-class therapeutic peptides are optimized analogues of a molecule that inhibits the GIP receptor that is naturally found in the human body. The market for weight loss drugs has exploded since the approval of Novo Nordisk’s GLP-1 receptor agonist, semaglutide, in 2021, followed by Eli Lilly’s combined GLP-1 and GIP agonist tirzepatide in 2022. Multiple companies are currently developing drugs with similar mechanisms of action with the goal of tapping into this rapidly growing market. googletag.cmd.push(function () { googletag.display('text-ad1'); }); Antag Therapeutics was founded in 2017 backed by a €2.7 million investment from Novo Seeds, the early-stage investment arm of Novo Holdings, which manages the assets of the Novo Nordisk Foundation. The company’s lead candidate, AT-7687, is a peptide GIP receptor antagonist, designed to be administered subcutaneously once a week. The development of this drug candidate is based on research by Professor Jens Juul Holst at the University of Copenhagen, co-founder of Antag Therapeutics and discoverer of GLP-1. Preclinical studies have shown that AT-7687 could reduce weight gain and enhance the weight loss effects mediated by GLP-1, which is the target of obesity drugs such as semaglutide. The drug has also shown potential to improve cholesterol profiles without causing gastrointestinal side effects.