The US Food and Drug Administration (FDA) has approved a 2.4 mg/week subcutaneous dose of the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide (Wegovy, Novo Nordisk) for weight loss.
Specifically, this drug format and dosage are approved as an adjunct to a reduced-calorie diet and increased physical activity to treat adults who have obesity (body mass index [BMI] ≥ 30 kg/m2) or are overweight (BMI ≥ 27 kg/m2) with at least one weight-related comorbidity.
Semaglutide “induces weight loss by reducing hunger, increasing feelings of fullness, and thereby helping people eat less and reduce their calorie intake,” according to a company statement.
“Gamechanger“ Drug Tested in STEP Clinical Trial Program
The favorable FDA ruling is based on results from the Semaglutide Treatment Effect in People With Obesity (STEP) program of four phase 3 clinical trials that tested the drug’s safety and efficacy in more than 4500 adults with overweight or obesity.
The four 68-week trials of subcutaneous semaglutide 2.4 mg/week versus placebo were published in the New England Journal of Medicine (STEP 1), The Lancet (STEP 2), and JAMA (STEP 3, STEP 4) in February and March 2021.
As previously reported by Medscape Medical News, all trials were in adults with overweight or obesity:
STEP 1 was in 1961 adults.
STEP 2 was in 1210 adults who also had diabetes.
STEP 3 was in 611 adults, where those in the treatment group also underwent an intensive lifestyle intervention.
STEP 4 was in 803 adults who had reached a target dose of 2.4 mg semaglutide after a 20-week run-in (and the trial examined further weight-loss in the subsequent 48 weeks).
In the STEP 1, 2, and 4 trials of individuals with overweight and obesity, those in the semaglutide groups attained a 15% to 18% weight loss over 68 weeks.
The dosage was well-tolerated. The most common side effects were gastrointestinal, and they were transient and mild or moderate in severity.
A coauthor of the STEP 1 trial, Rachel Batterham, MBBS, PhD, of the Centre for Obesity Research at University College London, UK, said at the time of publication: “The findings of this study represent a major breakthrough for improving the health of people 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,” she added.
Lower-Dose Injectable and Pill Already Approved for Diabetes
Subcutaneous semaglutide at doses up to 1 mg/week (Ozempic, Novo Nordisk), which comes as prefilled pens at doses of 0.5 mg or 1.0 mg, is already approved for the treatment of type 2 diabetes.
The company is also applying for approval for a higher dose of semaglutide, 2 mg/week, for use in type 2 diabetes, and has just resubmitted its label expansion application to the FDA, after the agency issued a refusal to file letter in March.
And in September 2019, the FDA approved oral semaglutide (Rybelsus, Novo Nordisk), in doses of 7 and 14 mg/day, to improve glycemic control in type 2 diabetes, making it the first GLP-1 receptor agonist available in tablet form.
CVOT and Oral Format Trials for Obesity on the Horizon
The ongoing Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial will shed light on cardiovascular outcomes after 2.5 to 5 years in patients with cardiovascular disease and overweight or obesity but without type 2 diabetes. Participants will receive semaglutide in doses up to a maximum of 2.4 mg/week, or placebo, as an adjunct to lifestyle recommendations focused on cardiovascular risk reduction. The study is expected to complete in 2023.
And Novo Nordisk plans to initiate a global 68-week phase 3 trial in the second half of 2021 on the efficacy and safety of oral semaglutide 50 mg compared with placebo in 1000 people with obesity or overweight and comorbidities.