Semaglutide – the drug that marked a new era in the management of obesity

A drug that suppresses appetite has been reported to be a major breakthrough in the management of overweight and obesity.

A weekly injection of the drug Semaglutide given alongside healthy lifestyle advice helped patients to lose significant amounts of weight. The STEP trial published in the high calibre scientific journal of the New England Journal of Medicine on 10^th February 2021 showed that:

• Three quarters (75%) of the patients who received Semaglutide lost more than 10% of their body weight.

• More than one-third lost (35%) of the study participants who received Semaglutide lost more than more than one-fifth (≥20%) of their total body weight.

• The average weight loss with Semaglutide treatment across all study participants was  ~15kg (almost 3 stone).

• The weight loss induced by Semaglutide was associated with reductions in risk factors for heart disease and diabetes, such as waist circumference, blood sugar levels and blood pressure and with reported improvements in overall quality of life.

To date bariatric surgery has been the only treatment option for achieving significant and sustainable weight loss effects. Following decades of scientific efforts for the successful management of the global obesity pandemic by medical means, Semaglutide now brings new hope to patients with overweight and obesity. Thus, Semaglutide is considered to be a “game-changer” and the “holy grail” for the management of obesity by medical means, without the need to undergo surgery.

Obesity has currently reached epidemic proportions globally, with more than 1 billion adults overweight – at least 300 million of them clinically obese. Obesity is in itself a risk factor for a number of serious and life-limiting health conditions including heart disease, type 2 diabetes mellitus, liver disease and certain types of cancers. Consequently, obesity is a major contributor to the global burden of chronic disease and disability and a major healthcare concern worldwide. Obesity has been identified as a risk factor for severe illness from Covid-19 infection, and hence the Covid-19 pandemic further highlighted the pressing need for effective drug therapies to combat the obesity crisis.

Semaglutide is already approved and used clinically at a lower dose for treatment of diabetes, so the medical community are familiar with the use of the drug in the clinical arena.

The STEP trial

 The STEP (Semaglutide Treatment Effect in People with obesity) Phase III study is an international, large scale randomised controlled trial published in the prestigious New England Journal of Medicine.  The study involved 1,961 adults with overweight or obesity. Average baseline weight across the study participants was 105kg/16.5 stone; average body mass index 38kg/m2. The trial was a multicentre international study with 129 sites in 16 countries across Europe, North America, South America and Asia.

Study participants received a 2.4mg dose of Semaglutide or placebo (dummy) weekly via injection under the skin in a similar way to which people with diabetes inject their insulin. Study participants also received individual counselling sessions from qualified dieticians every four weeks (either face-to-face or by phone), as well as relevant incentives, i.e. food scales or kettle bells.

Amongst those who received Semaglutide the average weight loss was 15.3kg (almost three stone), whereas the average BMI declined was 5.54kg/m2 compared to an average weight loss 2.6kg (0.4 stone) and an average BMI reduction of 0.92kg/m2 in those who received placebo (the dummy treatment).

In addition to the significant weight loss, patients who received Semagltuide also experienced improvements in risk factors for heart disease and diabetes, such as waist circumference, blood sugar levels and blood pressure, and improvement in perceived quality of life.

Semaglutide: about the drug

Semaglutide is clinically approved drug for the treatment of type 2 diabetes. However, the dose of Semaglutide used for the treatment of diabetes is lower, up to a maximum of 1mg weekly; whereas in the STEP trial participants received higher doses of Semaglutide (2.4 mg weekly).

Semaglutide contains a compound structurally similar to the human gut hormone glucagon-like peptide-1 (GLP-1) hormone. GLP-1 in a naturally occurring hormone, physiologically released from the distal gut into the blood stream following intake of nutrients (food consumption). GLP-1 is a key satiety mediator. It relays to the brain a feeling of fullness and satiety, thereby reducing the sense of hunger and food consumption/caloric intake.

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Dr Karra is a Consultant in Endocrinology and Diabetes at The Physicians’ Clinic, Princess Grace Hospital, The Harley Street Clinic and the Wellington Hospital.

Find out more about Dr Karra’s expertise