STEP 4: Long-term treatment needed for full semaglutide benefit
medwireNews: People with obesity continue to lose weight if they remain on semaglutide 2.4 mg after an initial 20 weeks of treatment, but gradually regain it if they switch to placebo, show the STEP 4 findings.
The trial participants lost an average 10.6% of their starting bodyweight during the 20-week run-in period. After randomization, this trend continued in those who continued to take semaglutide, who lost an average 7.9% of bodyweight between weeks 20 and 68, whereas those who switched to placebo regained an average of 6.9%.
This gave a 14.8 percentage point difference between the groups, which was statistically significant, report Domenica Rubino (Washington Center for Weight Management and Research, Arlington, Virginia, USA) and study co-authors.
Over the whole trial from start of the run-in to week 68, people taking semaglutide lost an average of 17.4% of their starting bodyweight, whereas those who switched to placebo lost just 5.0%.
The findings “are consistent with findings from other withdrawal trials of antiobesity medications [and] emphasize the chronicity of obesity and the need for treatments that can maintain and maximize weight loss,” the researchers write in JAMA.
Domenica Rubino discusses the chronicity of obesity, and how STEP 4 demonstrates the need for long-term semaglutide treatment to avoid weight regain (5:59).
A total of 902 people, who had obesity or overweight with at least one related comorbidity (but not type 2 diabetes), entered the run-in period. The semaglutide dose could be reduced to 1.7 mg/week if needed to aid tolerability, but with at least one attempt to re-escalate to the full 2.4 mg dose.
The 803 participants who achieved a stable semaglutide dose from at least week 16 were randomly assigned in a 2:1 ratio to continue with semaglutide or switch to placebo. These people were aged an average of 46 years, 79% were women, 84% were White, and their average bodyweight was 107 kg (average BMI=38.4 kg/m2).
Systolic blood pressure remained stable in the semaglutide group between weeks 20 and 68, whereas it rose in the placebo group, giving a significant 3.9 mmHg difference between the groups. And semaglutide was also associated with continued significant improvements in blood glucose and physical functioning during this period, when compared with placebo.
The researchers highlight these improvements in cardiometabolic risk factors, saying: “Sustained weight loss of a similar magnitude to that observed in this trial has been linked to improvements in obesity-related complications, such as type 2 diabetes, with treatment guidelines recommending sustained weight loss of 5% to 15% for people with these conditions.”
They add: “The sustained effects of semaglutide on body weight and cardiometabolic risk factors, as well as participants’ physical and mental functioning, indicate the potential for positive effects on such obesity-related complications.”
During the run-in phase, 84.3% of participants reported adverse events, with 71.4% reporting gastrointestinal events, and 5.3% discontinuing semaglutide, largely because of gastrointestinal events.
Study participants continued to report gastrointestinal events during the randomized phase, and this was more common among those taking semaglutide versus placebo, at 41.9% versus 26.1%.
However, the researchers note that most events were mild to moderate and resolved without the need for treatment discontinuation; just over 2% of participants discontinued during the randomized period.
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