The report says that 50% of the participants in the semaglutide groups demonstrated significant reductions in weight of 15% or more, 60% achieved 10% or more, and 86% lost 5% or more. Additionally, the trial demonstrated reductions in the risk factors for diabetes and heart disease along with greater self-reported physical functioning in those in the semaglutide group.
The global obesity epidemic continues to increase, this is a prevalent and serious health concern in America with the CDC reporting the prevalence of obesity in America increasing from 30.5% during 1999-2000 to reach 42.4% during 2107-2018, with the prevalence of severe obesity increasing from 4.7% to 9.2% during the same timeframes.
Body mass index/BMI is often used to determine if a person is at a healthy weight or not. To reach this number divide your weight in kilograms by the square of your height in meters. A BMI below 18.5 is underweight, 18.5 to 24.9 is normal, and a BMI of 25-30 falls within the overweight range in most adults, those with obesity have a BMI of 30 to 39.9, a BMI of 40 or higher suggests extreme/severe obesity.
Obesity should be taken seriously as it is a severe health concern reducing life expectancy and being a major risk factor for cardiovascular disease, type 2 diabetes, non-alcoholic fatty liver disease, and certain cancers. Diet and exercise are the mainstays to treat obesity, should these lifestyle interventions be ineffective for over 6 months certain clinical guidelines may recommend medications for those with a BMI greater than 30 or those with a BMI of 27 or greater with other related health conditions.
The use of current medications is limited by effectiveness, cost, and safety issues. One of the drugs that are currently approved by the FDA for adults with cardiovascular disease and type 2 diabetes is an injectable called semaglutide. This drug is an analog of the naturally occurring human glucagon-like peptide-1 hormone produced within the body, it is released from the gut into the bloodstream after meals to increase satiety and decrease hunger/cravings.
During a Phase 2 clinical trial adults with obesity and type 2 diabetes receiving the injectable semaglutide treatment experienced weight loss; this led to the global Phase 3 trial STEP to further investigate the safety and effectiveness of this drug in participants aged 18+ with a BMI greater than 30 or a BMI of 27 or higher and weight-related health conditions, along with a control placebo group.
In the Semaglutide Treatment Effect in People with Obesity trial those with diabetes, those who had previously undergone obesity surgery, or those using medications to treat obesity in the 90 days before enrollment were excluded from being participants. The participant did have some weight-related health conditions including cardiovascular disease, obstructive sleep apnea, high cholesterol, and hypertension. The trial involved a total of 1961 participants who were randomly assigned to the placebo group or the semaglutide group, with both groups receiving lifestyle interventions. Over the course of 68 weeks, 1306 participants received treatment, and 655 received a placebo on a weekly basis. At baseline the average body weight was 105.3 kg, the average BMI was 37.9, the average age was 46 years old, and 75% of the participants had at least one coexisting condition.
The researchers reported on average those in the treatment group significantly decreased body weight by 14.9% from baseline compared to the placebo group decreasing on average 2.4%. Significant weight reductions were demonstrated of 5% or greater in 86.4% of the participant in the semaglutide treatment group compared to 31.5% in the control placebo group; 10% or greater in 69.1% in the treatment group vs 12% in the placebo group; and 15% or greater in 50.5% of the participants in the treatment group compared to 4.9% in the placebo control group.
Participants in the treatment group also experienced greater reductions in waist circumference, blood pressure, fasting lipid levels, and blood glucose along with recording increases in self-reported physical functioning scores compared to that of those in the placebo group. The most common adverse effects included mild to moderate nausea and diarrhea that typically subsided with time.
The trial was limited by having a short duration, the exclusion of those with diabetes, and the majority of the participants being white females possibly limiting the generalizability of the findings to not be reflective of the general population of those with obesity.
“No other drug has come close to producing this level of weight loss — this really is a gamechanger. For the first time, people can achieve through drugs what was only possible through weight loss surgery,” said one of the main authors of the study, Rachel Batterham, M.B., B.S., Ph.D., a professor of obesity, diabetes, and endocrinology at the Centre for Obesity Research at University College London (UCL) and the UCL Hospitals Centre for Weight Management.
Based on these findings an application has been filed with the FDA, the European Medicines Agency, and the National Institute for Health and Care Excellence for regulatory approval for the injectable semaglutide to treat obesity by Novo Nordisk. While this trial does seem promising this process will require head-to-head trials comparing semaglutide with other standards of care pharmacologic and surgical treatment options to determine an eventual role in treatment.
“The impact of obesity on health has been brought into sharp focus by COVID-19, where obesity markedly increases the risk of dying from the virus, as well as increasing the risk of many life limiting serious diseases, including heart disease, type 2 diabetes, liver disease, and certain types of cancers,” adds Dr. Batterham. “This drug could have major implications for U.K. health policy for years to come.”
Prof Sir Stephen O’Rahilly, from the University of Cambridge, said: “The amount of weight loss achieved is greater than that seen with any licensed anti-obesity drug. “This is the start of a new era for obesity drug development with the future direction being to achieve levels of weight loss comparable to semaglutide, while having fewer side-effects.”
Dr. Duane Mellor, a dietitian and from Aston Medical School, said: “It is useful to have a potential option to help people lose weight, however, we need to acknowledge that weight loss will still need lifestyle change, and that any medication or change in lifestyle can bring potential risks and side-effects. “So, it is always wise to speak to a health professional before trying to lose weight.”
