- A Phase 3 clinical trial published in The New England Journal of Medicine showed a mean decrease of 14.9% in body weight in obese or overweight adults receiving an injectable diabetes medication, semaglutide, in addition to lifestyle interventions.
- About 50% of the participants in the semaglutide group achieved significant weight reductions of 15% or more, while 69% of the participants achieved 10% or more, and 86% of the participants achieved 5% or more.
- The trial showed a reduction in risk factors for diabetes and heart disease and a greater self-reported physical functioning in participants who received semaglutide.
Obesity is a common and serious health concern, both in the United States and worldwide. The Centers for Disease Control and Prevention (CDC) reports that the prevalence of obesity in the US has increased significantly from 30.5% in 1999-2000 to 42.4% in 2017–2018, with severe obesity rising from 4.7% rose to 9.2%.
Doctors often use body mass index (BMI) – which a person can calculate by dividing their weight in kilograms (kg) by dividing the square of their height in meters – to determine if a person’s weight is healthy. A BMI of 25 to
Obesity reduces life expectancy and is a major risk factor for cardiovascular disease, type 2 diabetes, non-alcohol-related fatty liver disease, and certain cancers, including breast, ovarian, endometrial, prostate, liver, and colon cancers.
Currently, a combination of diet and exercise is the mainstay of obesity treatment. If these lifestyle interventions over 6 months prove ineffective, clinical guidelines are recommended for people with a BMI of ≥30 or those with a BMI of ≥27 who have other related health conditions.
Issues of efficacy, cost and safety limit the use of currently available medicines. Injectable semaglutide is a drug approved by the Food and Drug Administration (FDA) for adults with type 2 diabetes and cardiovascular disease.
Semaglutide is an analogue of the natural human glucagon-like peptide-1 (GLP-1) hormone in the body. The body releases GLP-1 after meals from the intestines into the bloodstream, which increases satiety and reduces hunger and cravings.
In a phase 2 clinical trial in adults with type 2 diabetes and obesity, injectable semaglutide treatment resulted in weight loss.
This result led researchers to conduct a global Phase 3 trial called the Semaglutide Treatment Effect in People with Obesity (STEP) to investigate the safety and efficacy of semaglutide in participants 18 years and older.
The participants have a BMI of ≥30 or a BMI of ≥27 and weight-related health conditions. A group of participants received a placebo instead of the treatment.
The trial excluded people who had diabetes, who had previously undergone obesity surgery or had used medication to treat obesity in the 90 days before enrollment. However, the participants had some weight-related health conditions, including hypertension, high cholesterol, obstructive sleep apnea, and cardiovascular disease.
The researchers randomly assigned 1,961 participants to receive semaglutide (as an injection under the skin at a dose of 2.4 milligrams) or placebo, while both groups also received lifestyle interventions.
Over 68 weeks, 1,306 participants received semaglutide and 655 participants received the placebo weekly.
At the starting line, the mean body weight was 105.3 kg, the mean age was 46 years and the mean BMI was 37.9. In addition, 75% of participants had at least one concurrent condition.
On average, participants in the semaglutide group significantly reduced their body weight by 14.9% (1515.3 kg) from baseline compared with 2.4% (,62.6 kg) in the placebo group.
The trial showed significant weight loss of:
- 5% or more in 86.4% of the participants in the semaglutide group compared to 31.5% in the placebo group
- 10% or more in 69.1% of participants in the semaglutide group compared to 12% in the placebo group
- 15% or more in 50.5% of participants in the semaglutide group versus 4.9% in the placebo group
Study participants who received semaglutide also had greater decreases in waist circumference, blood pressure, fasting lipid levels, and blood glucose than those who received the placebo. In addition, they increased self-reported scores for physical functioning.
The most common side effects included mild to moderate nausea and diarrhea that usually subsided over time. More participants discontinued treatment due to gastrointestinal side effects in the semaglutide group (4.5%) than in the placebo group (0.8%).
The trial had some limitations, including the short duration and exclusion of people with diabetes.
The majority of participants were white (75.1%) and female (74.1%) and therefore did not reflect the general population with obesity. This limits the generalizability of the findings.
In addition, people with a phobia of needles do not want to use an injectable drug in the long run.
One of the lead authors of the study, Rachel Batterham, MB, BS, Ph.D., a professor of obesity, diabetes and endocrinology at the Center for Obesity Research at University College London (UCL) and the UCL Hospitals Center for Weight. Management comments on the findings:
‘No other remedy has produced near this weight loss – it’s really a game changer. For the first time, people can achieve through drugs that were only possible through weight loss surgeries. ”
Based on these trial results, Novo Nordisk, the pharmaceutical company funding the clinical trial, has applied for approval by the regulator of injectable semaglutide to treat obesity at the FDA, the European Medicines Agency and the National Institutes of Health and Care Excellence.
Although the trial results look promising, head-to-head trials comparing semaglutide with other standard pharmacological and surgical treatment options are needed to determine its ultimate role in treatment.
Dr Batterham adds: “The impact of obesity on health has been sharply highlighted by COVID-19, where obesity significantly increases the risk of dying from the virus, as well as increasing the risk of many diseases, including heart, many lives. “disease, type 2 diabetes, liver disease and certain types of cancers.”
“This remedy could hold many more years for British health policy.”