A 2.4-mg weekly injection of the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide led to a clinically meaningful 5% loss in weight for roughly two-thirds of patients with both overweight/obesity and type 2 diabetes, researchers report.
These findings from the Semaglutide Treatment Effect in People With Obesity 2 (STEP 2) trial, one of four phase 3 trials of this drug, which is currently under regulatory review for weight loss, were published March 2 in The Lancet.
More than 1,000 patients (mean initial weight, 100 kg [220 pounds]) were randomly assigned to receive a lifestyle intervention plus a weekly injection of semaglutide 2.4 mg or semaglutide 1.0 mg or placebo. At 68 weeks, they had lost a mean of 9.6%, 7.0%, and 3.4%, respectively, of their starting weight.
In addition, 69% of patients who had received semaglutide 2.4 mg experienced a clinically meaningful 5% loss of weight, compared with 57% of patients who had received the lower dose and 29% of patients who had received placebo.
The higher dose of semaglutide was associated with a greater improvement in cardiometabolic risk factors. The safety profile was similar to that seen with other drugs in this class.
“By far the best results with any weight loss medicine in diabetes”
Importantly, “more than a quarter of participants lost over 15% of their body weight,” senior author Ildiko Lingvay, MD, stressed. This “is by far the best result we had with any weight loss medicine in patients with diabetes,” Dr. Lingvay, of the University of Texas, Dallas, said in a statement from the university.
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Dr. Ildiko Lingvay
“The drug works by suppressing appetite centers in the brain to reduce caloric intake,” she explained. “The medication continually tells the body that you just ate, you’re full.”
Similarly, lead author Melanie J. Davies, MD, said that the STEP 2 results “are exciting and represent a new era in weight management in people with type 2 diabetes.
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Dr. Melanie J. Davies
“They mark a real paradigm shift in our ability to treat obesity,” with results closer to those achieved with bariatric surgery, Dr. Davies, of the University of Leicester, England, said in a statement from her institution.
“It is really encouraging,” she continued, “that along with the weight loss we saw real improvements in general health, with significant improvement in physical functioning scores, blood pressure, and blood glucose control.”
Dr. Lingvay noted that on average, patients in the four STEP clinical trials lost 10%-17% of their body weight, “which is a huge step forward compared with all other medications currently available to treat obesity.” She stressed that these results are comparable to the 20%-30% weight loss seen with bariatric surgery.
One of four trials under review
More than 90% of people with type 2 diabetes are overweight or have obesity, and more than 20% of people with obesity have diabetes, wrote Dr. Davies and colleagues.
Semaglutide (Ozempic), administered subcutaneously at a dose of 0.5 mg to 1 mg weekly, is approved by the Food and Drug Administration for the treatment of type 2 diabetes. Dosing studies indicated that it is associated with weight loss.
As previously reported, four trials of the use of semaglutide for weight loss (STEP 1, 2, 3, and 4) have been completed. The combined data were submitted to the FDA on Dec. 4, 2020 (a decision is expected within 6 months) and to the European Medicines Agency on Dec. 18, 2020.
The STEP 1 and STEP 3 trials of semaglutide 2.4 mg vs. placebo were recently published. The STEP 1 trial involved 1,961 adults with obesity or overweight; the STEP 3 trial, 611 adults with obesity or overweight. In each of the trials, some patients also underwent an intensive lifestyle intervention, and some did not. In both trials, patients with type 2 diabetes were excluded.
Topline results from STEP 2 were reported in June 2020.
STEP 2 enrolled patients with type 2 diabetes
STEP 2 involved 1,210 adults in 149 outpatient clinics in 12 countries in Europe, North America, South America, the Middle East, South Africa, and Asia. All participants had type 2 diabetes.
For all patients, the body mass index was ≥27 kg/m2, and the A1c concentration was 7%-10%. The mean BMI was 35.7 kg/m2, and the mean A1c was 8.1%.
The mean age of the patients was 55 years, and 51% were women; 62% were White, 26% were Asian, 13% were Hispanic, 8% were Black, and 4% were of other ethnicity.
Participants were managed with diet and exercise alone or underwent treatment with a stable dose of up to three oral glucose-lowering agents (metformin, sulfonylureas, SGLT2 inhibitors, or thiazolidinediones) for at least 90 days. They were then randomly assigned in 1:1:1 ratio to receive semaglutide 2.4 mg, semaglutide 1.0 mg, or placebo.
The starting dose of semaglutide was 0.25 mg/wk; the dose was escalated every 4 weeks to reach the target dose.
All patients received monthly counseling from a dietitian about calories (the goal was a 500-calorie/day deficit) and activity (the goal was 150 minutes of walking or stair climbing per week).
The mean A1c dropped by 1.6% and 1.5% in the semaglutide groups and by 0.4% in the placebo group.
Adverse events were more frequent among the patients who received semaglutide (88% and 82%) than in the placebo group (77%).
Gastrointestinal events that were mainly mild to moderate in severity were reported by 64% of patients in the 2.4-mg semaglutide group, 58% in the 1.0-mg semaglutide group, and 34% in the placebo group.
Semaglutide (Rybelsus) is approved in the United States as a once-daily oral agent for use in type 2 diabetes in doses of 7 mg and 14 mg to improve glycemic control along with diet and exercise. It is the first GLP-1 agonist available in tablet form.
The study was supported by Novo Nordisk. The authors’ relevant financial relationships are listed in the original article.
A version of this article first appeared on Medscape.com.