Zusammenfassung
In adults with overweight or obesity, continued treatment with OW s.c. semaglutide
2.4 mg led to clinically relevant weight loss, while switching to placebo led to significant
weight regain; these data underscore the chronicity and relapsing nature of obesity,
and the need for continued treatment.
Einleitung
In people with overweight or obesity, long-term maintenance of weight loss is challenging.
Subcutaneous (s.c.) semaglutide has shown clinically relevant weight loss in people
with obesity. STEP 4 investigated the impact of continued semaglutide 2.4 mg treatment,
vs. switching to placebo, on maintenance of weight loss.
Material und Methodik
This was a 68-week withdrawal trial in adults with body mass index (BMI)≥30 kg/m²
(or BMI≥27 kg/m² with≥1 weight-related comorbidity), without diabetes. Following a
20 week run-in period, 803 subjects who reached the maintenance dose of once-weekly
(OW) s.c. semaglutide 2.4 mg were randomised to continue treatment with semaglutide
2.4 mg or switch to placebo for 48 weeks, both as adjunct to lifestyle intervention.
The primary endpoint was percent change in body weight between randomisation (week
20) and week 68. Confirmatory secondary endpoints included change in waist circumference
and systolic blood pressure.
Ergebnisse
Mean body weight (±standard deviation) was 107.2±22.7 kg at week 0 and 96.1±22.6 kg
at randomisation (week 20). Randomised participants were mostly female (79%); mean
age was 46 years and mean BMI was 34.4 kg/m². Between weeks 20 and 68, estimated mean
body weight change was−7.9% vs.+6.9% for semaglutide 2.4 mg vs. placebo (estimated
treatment difference [ETD]:−14.8%; 95% confidence interval [CI]:−16.0,−13.5; p<0.0001),
and –8.8% vs.+6.5%, respectively). For participants randomised to continue semaglutide,
the estimated change in body weight from week 0 to 68 was –17.4%. Continued semaglutide
treatment (weeks 20 to 68) led to clinically relevant improvements in waist circumference,
systolic blood pressure, BMI, glycated haemoglobin, fasting plasma glucose and lipids
(total cholesterol, low-density lipoprotein, and triglycerides) vs. switching to placebo
(p<0.0001 for all). During the run-in period, 5.3% of participants discontinued treatment
due to adverse events; during the randomised period, 2.4% (semaglutide) and 2.2% (placebo)
discontinued. Nausea, diarrhoea and constipation (mostly transient and mild to moderate)
were the most frequent adverse events with semaglutide.
