The recently licensed weight-loss drug semaglutide 2.4 mg/week (Wegovy, Novo Nordisk) “is likely to usher in a new era in the medical treatment of obesity,” Lee M. Kaplan, MD, PhD, stated at the annual scientific sessions of the American Diabetes Association, held virtually.
Dr. Lee M. Kaplan
Dr. Kaplan discussed the clinical implications of caring for patients with obesity now that the glucagon-like peptide-1 (GLP-1) receptor agonist is approved in the United States for weight loss.
Weight loss with semaglutide 2.4 mg was twice that achieved with liraglutide 3 mg (Saxenda, Novo Nordisk) – that is, roughly a 10%-15% weight loss at 68 weeks, said Dr. Kaplan, who was not involved in the pivotal STEP clinical trials of the agent.
“I think as we start to see more data come in over the next couple of years,” including from the cardiovascular outcome trial SELECT, he continued, “we’ll be able to use the data to create a nuanced [individualized patient treatment] approach, but we’ll also be able to use our clinical experience, which will grow rapidly over the next few years.”
In the future, semaglutide is likely to be combined with other drugs to provide even greater weight loss, predicts Dr. Kaplan, director of the Obesity, Metabolism, and Nutrition Institute at Massachusetts General Hospital in Boston.
In the meantime, “to be effective, semaglutide needs to be used,” he stressed, while noting that responses to the drug vary by individual, and so this will need to be taken into account.
“Obesity needs to be recognized as a disease in its own right, as well as a risk factor for numerous other diseases, [and] equitable access to obesity treatment needs to be broadened,” he emphasized.
Four pivotal phase 3 trials
As previously reported, four pivotal 68-week, phase 3 clinical trials in the Semaglutide Treatment Effect in People With Obesity (STEP) program tested the safety and efficacy of subcutaneous semaglutide 2.4 mg/week in more than 4,500 adults with overweight or obesity.
The trials have been published in high profile journals – the New England Journal of Medicine (STEP 1), The Lancet (STEP 2), and JAMA (STEP 3 and STEP 4) – said Robert F. Kushner, MD.
“I would encourage all of you to download and read each of these trials on your own,” Dr. Kushner, professor of medicine and medicine education at Northwestern University, Chicago, and coauthor of STEP 1, said before presenting a top-level review of key results.
STEP 1 examined weight management, STEP 3 added a background of intensive behavioral therapy, STEP 4 investigated sustained weight management, and STEP 2 (unlike the others) investigated weight management in patients with type 2 diabetes, he summarized.
In STEP 1, patients who received semaglutide had an average 15% weight loss, and those who stayed on the drug had a 17% weight loss, compared with the 2.4% weight loss in the placebo group.
“One-third of individuals in the trial achieved at least a 20% weight loss or more,” Dr. Kushner said, which is “really phenomenal.”
The results of STEP 3 “suggest that semaglutide with monthly brief lifestyle counseling alone is sufficient to produce a mean weight loss of 15%,” he noted, as adding a low-calorie diet and intensive behavior therapy sped up the initial weight loss but did not increase the final weight loss.
A post hoc analysis of STEP 2 showed “it’s clear that improvement in A1c” is greater with at least a 10% weight loss versus a smaller weight loss, Dr. Kushner said. A1c dropped by 2.2% versus 1.3%, with these two weight losses, respectively.
In STEP 4, after dose escalation to 2.4 mg at 20 weeks, patients had lost 10.6% of their initial weight. At 68 weeks, those who were switched to placebo at 20 weeks had lost 5.4% of their initial weight, whereas those who remained on semaglutide had lost 17.7% of their initial weight.
This shows that “if you remove the drug, the disease starts to come back,” Dr. Kushner pointed out.
Nausea, the most common side effect, occurred in 20% of patients, but was mostly mild or moderate, and gastrointestinal effects including constipation, vomiting, and diarrhea were transient and occurred early in the dose escalation phase.