BAGSVÆRD, Denmark, May 13, 2021 /PRNewswire/ -- Novo Nordisk today announced new results from the STEP phase 3a clinical trial programme, demonstrating potential benefits beyond weight loss for people with obesity being treated with semaglutide 2.4 mg. The trial showed that treatment with once-weekly semaglutide 2.4 mg led to significant improvements in physical functioning, such as climbing stairs and tying your shoes, and beneficial effects on weight related and health related quality of life scores (HRQoL) compared to placebo.* Following the 68-week treatment period, more than half of participants had improved quality of life scores, indicating better physical function and improved psychological wellbeing.^[1] The results from the STEP 1 trial will be presented today at the virtual European Congress on Obesity (ECO) 2021 Annual Meeting.

"Weight management is much more than achieving weight loss. We should also aim to improve the impairments that accompany elevated weight such as decreased physical functioning," said Dr Sean Wharton of the Wharton Medical Clinic, Toronto, Canada and an investigator of this study. "It is encouraging to see that the significant weight loss achieved in STEP 1 had such a positive impact on people's wellbeing and their ability to perform daily physical activities, such as taking walks and going about their daily routines."

Obesity is becoming one of the most important global health concerns, with more than 650 million people living with obesity worldwide.^[2] The risk factors of obesity and overweight, such as increased risk of type 2 diabetes and cardiovascular disease, are well-documented. However, often obesity has a significant negative impact on people's wellbeing affecting their physical and psychological health and limiting their daily activities.^[3]

"I am really proud of these results. Obesity is not only about the weight itself; living with this chronic disease affects all aspects of a person's life such as not being able to climb stairs or move around as part of one's daily routines," said Martin Holst Lange, executive vice president, Development at Novo Nordisk. "This has implications both for physical and mental health. This study shows that treatment with semaglutide 2.4 mg improves mental and physical wellbeing. It holds real potential to improve the lives of people living with obesity."

Data Details

In the phase 3a STEP 1 trial, treatment with once-weekly semaglutide 2.4 mg over a 68-week period was associated with greater improvements for all weight- and health-related quality of life scores^(A) in people with obesity or overweight, compared to placebo. People on semaglutide 2.4 mg had an improved wellbeing such as feeling more energetic and more self-confident, with 43.8% achieving a clinically meaningful improvement in total weight-related quality of life score^(B) at week 68. In addition, more than half of people (51.2%) treated with semaglutide 2.4 mg had an increased weight-related physical function score indicating improvements in the ability to perform daily physical activities such as tying their shoe and walking to the shops. These improvements occurred simultaneously with the significant weight loss of 14.9% (16.9% with the trial product estimand) observed with semaglutide 2.4 mg over more than a year.^[4] 

The safety profile of semaglutide 2.4 mg is in line with observations seen previously with glucagon-like peptide-1 (GLP-1) receptor agonists. Semaglutide 2.4 mg is generally well-tolerated, and the most common adverse events among people treated with semaglutide 2.4 mg were gastrointestinal events.^[1,5] 

About STEP 1 and the STEP clinical trial programme

STEP 1 was a 68-week phase 3a randomised, double-blind, multicentre, placebo-controlled trial that investigated the percentage change in body weight and the number of people achieving 5% or more weight reduction with subcutaneous semaglutide 2.4 mg versus placebo, in conjunction with lifestyle intervention. The trial was designed to assess the effect of once-weekly semaglutide 2.4 mg plus lifestyle intervention on sustained, clinically relevant reduction in body weight in adults with a body mass index of ≥30 or ≥27 in people with ≥1 weight-related coexisting condition. Participants were randomly assigned (in a 2:1 ratio) to 68 weeks of treatment with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo, plus lifestyle intervention (counselling and a reduced-calorie diet together with 150 minutes per week of physical activity).^[1,5]

STEP (Semaglutide Treatment Effect in People with obesity) is a phase 3 clinical development programme with once-weekly subcutaneous semaglutide 2.4 mg in obesity. The global clinical phase 3a programme consists of four trials and has enrolled approximately 4,500 adults with overweight or obesity.^[6] In the STEP trials, the primary estimand (treatment policy estimand) assessed effects regardless of treatment adherence or initiation of other anti-obesity therapies. The secondary estimand (trial product estimand) assessed effects if all people adhered to treatment and did not initiate other anti-obesity therapies.

In the phase 3a STEP 1 trial, people on semaglutide 2.4 mg experienced significant improvements in weight-related quality of life, with 43.8% achieving clinically meaningful improvement in total weight-related quality of life score^(B) of ≥16.6 points at week 68. In addition, 51.2% of people treated with semaglutide 2.4 mg achieved clinically meaningful improvement in weight-related physical function score (≥14.6 points) compared to 32.9% with placebo. Changes in health-related quality of life scores^(C), such as physical functioning and social functioning, were higher and favoured semaglutide versus placebo.^[5] Similarly, 40% of participants achieved clinical meaningful improvement in health-related physical functioning score (≥3.7 points), compared to 27% with placebo.^[1,5] These improvements were observed using patient-reported outcome methods commonly used in clinical trials for people with obesity.

About subcutaneous semaglutide 2.4 mg for weight management

Once-weekly semaglutide 2.4 mg is under investigation for chronic weight management and not yet approved for people with obesity. It is currently under regulatory review in several countries, including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

Semaglutide is an analogue of the human glucagon-like peptide-1 (GLP-1) hormone, with 94% similarity to the native human GLP-1 molecule.^[7,8] It induces weight loss by reducing hunger, increasing feeling of fullness and thereby helping people eat less and reduce their food cravings.^[7]

About obesity

Obesity is a chronic disease that requires long-term management.^[9,10] It is associated with many serious health complications and decreased life expectancy.^[11,12] Obesity-related complications are numerous and include type 2 diabetes,^[10] heart disease,^[10] obstructive sleep apnoea,^[13] non-alcoholic fatty liver disease^[14] and certain types of cancer.^[15] The current COVID-19 pandemic has highlighted that obesity also increases the risk for severe illness and hospitalisation due to COVID-19.^[16,17] 

The global increase in the prevalence of obesity is a public health issue that has severe cost implications to healthcare systems. In 2016, 13% of adults, or approximately 650 million adults, were living with obesity worldwide.^[18]

About Novo Nordisk

Novo Nordisk is a leading global healthcare company, founded in 1923 and headquartered in Denmark. Our purpose is to drive change to defeat diabetes and other serious chronic diseases such as obesity and rare blood and endocrine disorders. We do so by pioneering scientific breakthroughs, expanding access to our medicines and working to prevent and ultimately cure disease. Novo Nordisk employs about 45,800 people in 80 countries and markets its products in around 170 countries. For more information, visit novonordisk.com, Facebook, Twitter, LinkedIn, YouTube. 

*The STEP trial participants were adults with a body-mass index of 30 or greater (Obesity) (≥27 in persons with ≥1 weight-related coexisting condition (overweight).

A. Weight and health related quality of life improvements were assessed using patient reported outcomes tools including Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT) and Short Form 36 (SF-36) questionnaires
B. IWQOL-Lite-CT is a questionnaire assessing the effect of weight on various areas of life such as physical function, self-esteem, public distress, sexual life and work; scores range from 0 to 100, with higher scores indicating better levels of functioning
C. SF-36 is a 36-item questionnaire evaluating health-related quality of life including physical functioning, bodily pain, role limitations due to physical health problems, emotional well-being, and social functioning; scores range from 0 to 100, with higher scores indicating favourable health status.

References:

1. Wharton S, Bjorner JB, Kushner RF, et al. Semaglutide 2.4 mg Once Weekly Improves Patient-Reported Outcome Measures of Physical Functioning in Adults with Overweight or Obesity in the STEP 1 Trial. Presented at ECO 2021, May 10-13.
2. World Health Organization. Obesity and Overweight Factsheet no. 311. Available at: http://www.who.int/mediacentre/factsheets/fs311/en/. Last accessed: May 2021.
3. Phelan S, Burgess DJ, Yeazel MW, et al. Impact of weight bias and stigma on quality of care and outcomes for patients with obesity. Obesity Reviews. 2015; 16:319-326.
4. Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021; 384:989.
5. Rubino DM, Bjorner JB, Kushner RF, et al. Beneficial Effect of Semaglutide 2.4 mg Once Weekly on Patient-Reported Outcome Measures of Weight-Related and Health-Related Quality of Life in Adults With Overweight or Obesity in the STEP 1 Trial. Presented at ECO 2021, 10-13 May.
6. Kushner RF, Calanna S, Davies M, et al. Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5. Obesity. 2020; 28:1050-1061.
7. Blundell J, Finlayson G, Axelsen M, et al. Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity. Diabetes Obes Metab. 2017; 19:1242-1251.
8. Lau J, Bloch P, Schaffer L, et al. Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide. J Med Chem. 2015; 58:7370-7380.
9. Wadden TA, et al. Intensive Behavioral Therapy for Obesity Combined with Liraglutide 3.0 mg: A Randomized Controlled Trial. Obesity 2019;21:75–86.
10. WHO. Obesity: Preventing and managing the global epidemic. Available at: http://www.who.int/iris/handle/10665/42330. Last accessed: May 2021.
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12. Guh DP, Zhang W, Bansback N, et al. The incidence of co-morbidities related to obesity and overweight: a systematic review and meta-analysis. BMC Public Health. 2009; 9:88.
13. Gami AS, Caples SM and Somers VK. Obesity and obstructive sleep apnea. Endocrinology and Metabolism Clinics of North America. 2003; 32:869-894.
14. Vernon G, Baranova A and Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011; 34:274-285.
15. Whitlock G, Lewington S, Sherliker P, et al. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet. 2009; 373:1083–1096.
16. Finer N, Garnett SP and Bruun JM. COVID-19 and obesity. Clin Obes. 2020; 10:e12365.
17. Ryan DH, Ravussin E and Heymsfield S. COVID 19 and the Patient with Obesity - The Editors Speak Out. Obesity (Silver Spring). 2020; 28:847.
18. Durrer Schutz D, Busetto L, Dicker D, et al. European Practical and Patient-Centred Guidelines for Adult Obesity Management in Primary Care. Obes Facts. 2019; 12:40-66.

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