The uncertain quest for a safe and effective drug to achieve long term weight loss has taken a promising step forward with results from a one year clinical trial of the glucagon-like peptide-1 (GLP-1) analogue semaglutide.

Obese people who received once-weekly subcutaneous of semaglutide achieved an average 12% loss in body weight over 68 weeks as part of a multinational placebo-controlled trial.

Published in the NEJM, the initial results of the Semaglutide Treatment Effect in People with Obesity (STEP) 1 trial, were derived from 1961 patients with a BMI of 30 or higher who received a weekly injection  of 2.4 mg semaglutide or placebo in addition to a lifestyle intervention.

The primary endpoint of mean change in body weight was 14.9% with the active drug and −2.4% with placebo, representing a difference of −12.4% for the GLP-1 agonist. In terms of actual weight loss this translated into a drop of 15.3 kg in the semaglutide group and 2.6 kg in the placebo group.

The co-primary endpoint of  losing 5% of more of body weight was achieved by 86.4% of those taking semaglutide as compared with 31.5% patients in the placebo group).

Furthermore, around 69% of patients in the semaglutide group had weight loss of 10% or more as compared with 12% in the placebo group.

Secondary endpoints of changes in cardiometabolic risk factors such as waist circumference, systolic BP, lipids and glycated haemoglobin also favoured semaglutide.

Patients who lost weight also showed improvements in physical function and quality of life.

Adverse events seen with semaglutide were similar to those known from its use in type 2 diabetes  and were mostly gastrointestinal: nausea, vomiting, and diarrhoea, which were seen in 74.2% of those taking active drug vs. 47.9% of the placebo groups

Gallbladder-related disorders, mainly cholelithiasis, also occurred more often in the semaglutide group.

The investigators of the study, funded by Novo Nordisk, said the findings showed semaglutide had potential as an antiobesity agent with a relatively infrequent dosing schedule compared to those that had to be taken on a daily basis.

An accompanying commentary said the results were promising for a field that had a troubling history of anti-obesity drugs being launched and then withdrawn due to adverse safety profile or lack of long term effect.

However it cautioned that the study population was not representative of the general population as there were few black and ethnic minority participants and conversely many had prediabetes.

Other questions related to the acceptability of weekly injections compared to oral medications and the effectiveness and safety of semaglutide when compared to other diabetes agents know to achieve weight loss such as SGLT-2 inhibitors.

“Similarly, given the effectiveness of bariatric surgery in regard to both weight loss and glucose tolerance, studies comparing these two distinct forms of therapy (surgery and pharmacologic therapy) will be required. In sum, we have a long way to go to control the obesity epidemic, but STEP 1 serves its name well,” the commentary authors concluded.