Novo Nordisk has shared additional results from clinical trials of Wegovy (semaglutide), a drug for treating obesity and overweight.
Wegovy was approved in June 2021 by the U.S. Food and Drug Administration (FDA) for long-term use to correct body weight in adult patients with obesity or overweight (with at least one weight-related comorbid condition). Wegovy should be prescribed as an adjunct to a low-calorie diet and increased physical activity.
A decision by the European Medicines Agency (EMA) will follow soon.
Semaglutide can help you lose 15% of your excess weight in a year. And even more.
Wegovy is now considered the most effective pharmacological approach to weight loss, the use of which, combined with changes in eating behavior and lifestyle, can relatively quickly and safely lose dozens of extra pounds. In general, its therapeutic effectiveness in the fight against obesity is twice that of other weight-loss drugs: at least 20% of weight is lost by every third patient taking Wegovy.
Wegovy is prescribed in the form of subcutaneous injections once a week.
The STEP 5 (NCT03693430) phase 3b clinical trial studied for two years the treatment of obesity or overweight with Wegovy among patients without type 2 diabetes mellitus.
The weekly addition of Wegovy to a low-calorie diet (minus 500 kcal per day) and increased physical activity (150 minutes per week) resulted in a mean weight loss of 15.2% — versus its reduction of 2.6% in the placebo group: the difference was −12.6% (95% CI: −15.3 to −9.8; p<0.0001).
- If subjects strictly adhered to Wegovy (did not skip doses, controlled eating behavior, exercised appropriately), the results were even better: weight loss was 16.7% — vs. 0.6%: a difference of −16.0% (95% CI: −18.6 to −13.5; p<0.0001).
Loss of at least 5% excess weight was recorded in 77% of patients receiving semaglutide — vs. 34% of subjects in the control group (p<0.0001). A loss of at least 10%, 15%, and 20% of kilograms was recorded among 62%, 52%, and 36% of people in the Wegovy group — vs. 13%, 7%, and 2% in the placebo group (p<0.0001).
And while 51% of patients were initially prediabetic before Wegovy treatment, only 20% were prediabetic at the end of therapy.
Administration of semaglutide provided statistically significant (p<0.05) improvement in the overall picture with cardiovascular and metabolic risk factors such as waist circumference, systolic and diastolic blood pressure, C-reactive protein, glycated hemoglobin (HbA1c), fasting plasma glucose, fasting serum insulin, and triglycerides.
A retrospective analysis of the results of STEP 1 (NCT03548935) and STEP 2 (NCT03552757) phase 3 clinical trials among patients with class II obesity (body mass index [BMI] ranging from 35 to 40 kg/m2) and weight-related comorbid condition or class III obesity (BMI 40 kg/2 or more) found that administration of Wegovy for 68 weeks was reflected in weight reductions of a mean of 13.9% and 10.6% in STEP 1 and STEP 2, respectively — versus reductions of 2.1% and 4.2% in the placebo groups: the difference was −11.8% (95% CI: −13.1 to −10.6) and −6.4% (95% CI: −8.0 to −4.8).
Administration of semaglutide provided statistically significant (p<0.05) improvement in the overall picture with cardiovascular and metabolic risk factors such as BMI, waist circumference, systolic blood pressure, C-reactive protein, and HbA1c.
The STEP 8 (NCT04074161) phase 3b clinical trial compared weekly administration of Wegovy with daily administration of Saxenda (liraglutide) among overweight or obese patients on a low-calorie diet (minus 500 kcal per day) and increased physical activity (150 minutes per week).
After 68 weeks, excess weight loss in the semaglutide group was a mean of 15.8% — versus 6.4% in the liraglutide group: the difference was −9.4% (95% CI: −12.0 to −6.8; p<0.001).
- If subjects strictly adhered to Wegovy or Saxenda (did not skip doses, controlled eating behavior, exercised appropriately), the results were even better: weight loss was 17.1% — vs. 6.6%: a difference of −10.5% (95% CI: −12.8 to −8.1; p<0.0001).
Treatment of obesity or overweight with semaglutide resulted in a greater proportion of subjects than among those who received liraglutide showing weight reductions of 10% or more (71% of patients — versus. 26%), 15% or more (56% vs. 12%), 20% or more (39% vs. 6%) [p<0.001].
Wegovy compared with Saxenda statistically significantly (p<0.001) improved overall picture with cardiovascular and metabolic risk factors such as waist circumference, HbA1c, diastolic blood pressure, and C-reactive protein.
Wegovy: What’s Next
Wegovy’s successes are remarkable. People who are obese or overweight try, on average, seven times to get rid of the fat deposits on their own before they seek qualified medical help. But even after desired weight loss, it often comes back, which is why options that help prevent getting fat again are important. New clinical results have confirmed the long-term effectiveness of Wegovy. Nevertheless, the prescription of semaglutide needs to be further monitored to definitively verify its long-term benefit so that proper conclusions can be drawn about the justification of lifelong therapy for obesity as a chronic disease.
The large-scale SELECT (NCT03574597) phase 3 clinical trial is ongoing and will answer the question of whether Wegovy can reduce the risk of major adverse cardiovascular events (MACE; cardiovascular death, nonfatal myocardial infarction, nonfatal stroke) in patients (n=17500) who are obese or overweight and have a history of cardiovascular disease (myocardial infarction, ischemic or hemorrhagic stroke, peripheral artery disease). Results covering a period of 2.5 to 5 years of treatment will be collected by fall 2023.
In parallel, the 52-week STEP-HFpEF (NCT04788511) phase 3 clinical trial testing the hypothesis that Wegovy will have beneficial effects in obese patients (BMI ≥30 kg/m2) diagnosed with heart failure (NYHA class II–IV) with preserved ejection fraction (HFpEF).
Wegovy is also being studied in the treatment of non-alcoholic steatohepatitis (NASH), liver disease in the development of which overweight or obesity plays a special role. The NCT04822181 phase 3 clinical trial will continue through 2028.
Two-year effect of semaglutide 2.4 mg vs placebo in adults with overweight or obesity: STEP 5. [PDF]
Two-year effect of semaglutide 2.4 mg on control of eating in adults with Overweight/obesity: STEP 5. [PDF]
Weight loss outcomes with semaglutide 2.4 mg in moderate or severe obesity in STEP 1 and 2. [PDF]
Semaglutide 2.4 mg vs liraglutide 3.0 mg for weight management in overweight or obesity (STEP 8). [PDF]