“A new era” for obesity drugs: Semaglutide helps slash 20% of body weight in Novo Nordisk-backed trial

11 Feb 2021 --- Semaglutide as an obesity treatment has been submitted for US, UK and EU regulatory approval following the revelation that it can help people lose over 20 percent of their body weight.

A Phase III trial of nearly 2,000 people was funded by Novo Nordisk, a Denmark-based healthcare company specializing in diabetes.

“This is a significant advance in the treatment of obesity. Semaglutide is already approved and used clinically at a lower dose for treatment of diabetes, so as doctors we are already familiar with its use,” says the trial’s UK chief investigator, John Wilding, who is a professor at the University of Liverpool.

“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,” adds Rachel Batterham, a principal author on the paper. 

She is also the professor of obesity, diabetes and endocrinology who leads the Centre for Obesity Research at UCL and the UCLH Centre for Weight Management, UK.

The researchers emphasize that these findings could play a major part in helping the UK to reduce the impact of diseases, such as COVID-19.

“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,” says Batterham.

“[Obesity also increases] the risk of many life-limiting serious diseases including heart disease, Type 2 diabetes, liver disease and certain types of cancers. This drug could have major implications for UK health policy for years to come,” she continues.The average trial participant receiving semaglutide lost 15.3 kg.

Significant weight loss
This latest trial, called Semaglutide Treatment Effect in People with Obesity (STEP), saw 75 percent of people who received semaglutide lose over 10 percent of their body weight. Additionally, more than one-third of participants lost more than 20 percent of their body weight. 

The average trial participant receiving semaglutide lost 15.3 kg, with a reduction in BMI of -5.54. This was accompanied by reductions in risk factors for heart disease and diabetes, such as waist circumference, blood fats, blood sugar and blood pressure and reported improvements in their overall quality of life.

In comparison, the placebo group lost an average of 2.6 kg, with a BMI reduction of -0.92. 

Reducing hunger
Semaglutide works by hijacking the body’s own appetite-regulating system in the brain leading to reduced hunger and calorie intake.

Specifically, the drug possesses a compound structurally similar to (and mimics) the human glucagon-like peptide-1 (GLP-1) hormone, which is released into the blood from the gut after meals.

GLP-1 induces weight loss by reducing hunger, increasing feelings of fullness and thereby helping people eat less and reduce their calorie intake.Each week, a 2.4 mg dose of semaglutide was administered via subcutaneous injections.

An international cohort
The randomized controlled trial involved 1,961 adults who were either overweight or had obesity. It took place at 129 sites in 16 countries across Asia, Europe, North America and South America.

Participants took a 2.4 mg dose of semaglutide (or matching placebo) weekly via subcutaneous (under the skin) injection. This is similar to the way people with diabetes inject insulin. 

Those taking part also received individual face-to-face or phone counseling sessions from registered dietitians every four weeks to help them adhere to the reduced-calorie diet and increased physical activity, providing guidance, behavioral strategies and motivation. 

Additionally, participants received incentives such as kettlebells or food scales to mark progress and milestones.

“Transient” side effects 
The STEP study has been through Phase I and II trials, assessing the 2.4 mg doses for safety. While semaglutide is clinically approved to be used for patients with Type 2 diabetes, it is typically prescribed in much lower doses of 1 mg.

Some participants in the Phase III trial reported side effects from the drug, including mild-to-moderate nausea and diarrhea. However, these were transient and generally resolved without permanent discontinuation from the study.

“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,” comments Sir Stephen O’Rahilly. He is the director of the MRC metabolic diseases Unit at the University of Cambridge, UK, and was not involved in the study.It remains to be seen whether the treatment remains effective in the long-term.

A long-term solution?
Semaglutide has now been submitted for regulatory approval as an obesity treatment to the UK’s National Institute of Clinical Excellence (NICE), the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA).

However, experts who were not involved in the original trial have flagged the importance of gathering more data on the long-term impacts. 

Keith Frayn, Emeritus Professor of human metabolism at the University of Oxford, UK, says that it will now be crucial to gather longer-term data to see if that weight loss can be maintained.

“While this study shows that patients on active treatment do lose a lot of weight, it does not show what happens when treatment stops,” adds Tom Sanders, Professor Emeritus of nutrition and dietetics at King’s College London, UK.

“The challenge post weight loss is to prevent a regain in weight. While a drug like this may prove useful in the short-term for obtaining rapid weight loss in severe obesity, they are not a magic bullet for preventing or treating less severe degrees of obesity,” Sanders explains.

Dr. Duane Mellor, senior teaching fellow at the Aston Medical School, also points out that the weekly injection of semaglutide did not lead to weight loss on its own as people changed their lifestyles as well.

“All participants in the study followed a 500 kcal per day energy deficit and were encouraged to increase physical activity to 150 minutes per week. So, it is perhaps better to say this semaglutide can support someone’s efforts to lose weight, and perhaps helps them to lose more weight than they would have done otherwise,” he concludes. 

By Katherine Durrell