STEP 8: Semaglutide better than liraglutide at weight-management doses
medwireNews: Semaglutide 2.4 mg produces substantially more weight loss than liraglutide 3.0 mg in people with overweight or obesity but without diabetes, say the STEP 8 investigators.
“However, the variability in treatment response means an individual’s tolerance and sensitivity to a specific treatment is important for obesity management,” they write in JAMA.
“Therefore, having multiple antiobesity medications proven to lower body weight through different mechanisms, with different adverse effect profiles and dosing regimens, can only benefit clinicians and patients.”
Domenica Rubino (Washington Center for Weight Management and Research, Arlington, Virginia, USA) and study co-authors randomly assigned the STEP 8 participants (average age 49 years, 78.4% women) to receive weekly semaglutide 2.4 mg (n=126), daily liraglutide 3.0 mg (n=127), or matching placebo injections (n=85).
The target doses were attained during escalation periods lasting 16 and 4 weeks for semaglutide and liraglutide, respectively, and the trial participants were followed up for a total of 68 weeks.
During this period, the average bodyweight reduction was 15.8% with semaglutide versus 6.4% with liraglutide. This equated to an average 15.3 and 6.8 kg decrease, from a starting bodyweight of 102.5 and 103.7 kg, respectively.
Significantly more people lost at least 10% of their starting bodyweight with semaglutide than liraglutide, at 70.9% versus 25.6%, and the same was true for at least 15% bodyweight loss, at a corresponding 55.6% versus 12.0%, and at least 20% bodyweight loss, at 38.5% versus 6.0%.
The researchers note that although both medications work by reducing energy intake, “the reduction in caloric intake vs placebo appears to be larger with semaglutide (35%) than liraglutide (approximately 16%).”
They add: “Semaglutide has also been associated with reductions in food cravings, which is less evident with liraglutide, suggesting different mechanisms of energy intake regulation.”
People taking semaglutide also had significantly greater improvements in a range of secondary outcomes than those taking liraglutide, which included waist circumference, lipid levels, glycated hemoglobin, and C-reactive protein level.
Adverse events were as expected for the medication class, with gastrointestinal side effects predominating, but being mostly transient and of mild-to-moderate severity.
More people discontinued liraglutide (12.6%) because of adverse events than semaglutide (3.2%) or placebo (3.5%), and overall discontinuations followed the same pattern, at 27.6%, 13.5%, and 17.6%, respectively.
The researchers suggest that the higher rate of liraglutide discontinuations could be partly because it was discontinued in the event of poor tolerance, and if restarted the dose had to be escalated again to remain in line with the approved prescribing recommendations. Semaglutide, on the other hand, was simply given at a lower dose.
In addition, they say the shorter half-life of liraglutide, “potentially causing a more abrupt, and thus noticeable, return in hunger,” could have affected participants’ perspectives of efficacy and thus contributed to discontinuations, as well as the need for daily rather than weekly administration.
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