Once weekly injection of the type-2 diabetes drug semaglutide (Ozempic) was associated with sustained, clinically meaningful weight loss in overweight or obese study participants without diabetes in the Novo Nordisk-sponsored STEP 1 clinical trial.
At 68 weeks, study participants treated with 2.4 mg of semaglutide weekly plus lifestyle intervention had lost, on average, roughly 15% of their body weight, while the average weight loss among placebo + lifestyle intervention participants was 2.4%.
In all, 85.4% of semaglutide-treated patients lost 5% or more of body weight, compared to 31.5% of placebo-treated patients during the study, and just over half (50.5%) lost 15% or more of body weight, compared to roughly 5% of those in the placebo arm of the study.
Semaglutide-treated participants also showed greater improvements in cardiometabolic risk factors and a greater increase in participant-reported physical functioning from baseline.
“The 14.9% mean weight loss that we observed in the semaglutide group is substantially greater than the weight loss of 4.0% to 10.9% from baseline with approved anti-obesity medications,” wrote researcher Robert Kushner, MD, of Northwestern University Feinberg School of Medicine, Chicago, and researchers
The findings were published online Feb. 10 ahead of print in the New England Journal of Medicine.
“Moreover, 86% of participants who received semaglutide, as compared with 32% of those who received placebo, lost 5% or more of baseline body weight, a widely used criterion of clinically meaningful response,” Kushner and colleagues wrote.
They further noted that weight loss with semaglutide appeared to be due to decreased energy intake associated with decreased appetite.
However, a commentary published with the study cautioned that the one-shot approach may not be a game changer since the study participants were mostly White women.
NEJM deputy editor Julie Ingelfinger, MD, and associate editor Clifford Rosen, MD, wrote that this lack of diversity, along with the fact that 40% of study participants were pre-diabetic, “raise additional questions about the efficacy of subcutaneous semaglutide in persons with obesity and normal glucose tolerance.”
They further noted that the findings do not address long-term efficacy and they questioned whether a once-weekly subcutaneous injection “would be a palatable or cost-effective solution (to obesity) in the long run,” adding that daily oral semaglutide — approved by the FDA as a type 2 diabetes drug in the fall of 2019 — “might be far more appealing to many people.”
“Moving forward, head-to-head trials comparing oral GLP-1 agonists with SGLT-2 antagonists or other weight-loss medications will be necessary,” they wrote.
They concluded that, given the effectiveness of bariatric surgery in regard to both weight loss and glucose tolerance, studies comparing surgery and pharmacologic interventions are also needed.
“In sum, we have a long way to go to control the obesity epidemic, but STEP 1 serves its name well,” Ingelfinger and Rosen wrote.
The STEP 1 study enrolled 1,961 adults who did not have diabetes with either body mass index (BMI) ≥30 or BMI ≥27 plus one or more weight-related preexisting conditions. Participants were randomly assigned in a 2:1 ratio to 68 weeks of once-weekly subcutaneous semaglutide at a dosage of 2.4 mg, or placebo. All participants received lifestyle interventions.
Primary endpoints included total percentage change in body weight at 68 weeks and weight reduction of at least 5%.
Among the main study findings:
- From baseline to 68 weeks the mean decline in body weight was −14.9% and −2.4% among the semaglutide and placebo groups, respectively, for an estimated treatment difference of −12.4% (95% CI, −13.4% to −11.5%; P<0.001).
- 1,047 participants (86.4%) in the active treatment group lost 5% or more of their body weight, compared to 182 (31.5%) in the placebo group.
- Sixty nine percent and 12%, respectively, in the semaglutide and placebo groups had lost 10% or more of their body weight, and 50.5% and 4.9% lost 15% or more at week 68 (P<0.001 for 5.%, 10% and 15%).
- The average reduction in in body weight was close to 34 pounds (−15.3 kg) in the semaglutide group and 5.7 pounds (−2.6 kg) in the placebo group, for an estimated treatment difference of close to 28 pounds (12.7 kg).
Semaglutide-treated patients showed greater improvements in cardiometabolic risk factors, including fasting plasma glucose (−8.35 mg/dL versus -0.48 mg/dL), diastolic blood pressure (−2.83 mm Hg versus −0.42 mm Hg) and glycated hemoglobin (−0.45% versus −0.15%). In a sub-population of patients with pre-diabetes, change in glycated hemoglobin at 68 weeks was −0.52% in the active treatment group and −0.17% with placebo.
Nausea and diarrhea were the most commonly reported adverse events with semaglutide. These symptoms were typically transient and of mild-to-moderate severity. Gallbladder-related disorders (mostly cholelithiasis) were reported in 2.6% and 1.2% of participants in the semaglutide and placebo groups, respectively. A total of 1.4% and 0.0%, respectively, experienced serious gastrointestinal events.
A total of 4.5% of those in the semaglutide and 0.8% in the placebo group discontinued treatment due to gastrointestinal events.
The researchers noted that the average weight reduction of 12.4% with once-weekly 2.4 mg semaglutide was significantly greater than the weight loss reported in a pivotal trial of the approved GLP-1 receptor agonist weight loss drug liraglutide, which is given as daily subcutaneous injections.
In that trial, at 56 weeks, patients in the liraglutide group had lost a mean of 8.4±7.3 kg of body weight, and those in the placebo group had lost a mean of 2.8±6.5 kg (a difference of −5.6 kg; 95 CI, −6.0 to −5.1; P<0.001).
STEP 1 study strengths included the large sample size and high rates of adherence and study completion. Limitations included a relatively homogeneous population. Just 26% of the participants were male, 6% were Black and 12% Latinx.
Once weekly injections of the type-2 diabetes drug semaglutide (Ozempic) was associated with sustained, clinically meaningful weight loss in overweight or obese study participants without diabetes in the STEP 1 trial.
A total of 85.4% of semaglutide-treated patients lost 5% or more of body weight, compared to 31.5% of placebo-treated patients.
Salynn Boyles, Contributing Writer, BreakingMED™
This research was funded by Novo Nordisk.
Lead researcher John Wilding reported receiving speaking fees and other fees from various pharmaceutical companies including AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen Global Services, Novo Nordisk, Sanofi Pasteur, Takeda and Wilmington Healthcare. Dr. Wilding also reported being president of the World Obesity Federation. Corresponding researcher Robert Kushner reported serving as a consultant for Novo Nordisk.
Editorial writers Julie Ingelfinger and Clifford J. Rosen are both employed as editors at New England Journal of Medicine.
Cat ID: 13
Topic ID: 76,13,730,13,795,192,518,669,772,94,917,918,925