Maintenance Semaglutide Injection Aids Continued Weight Loss

Adults with overweight or obesity who take semaglutide injections for 20 weeks to lose weight are more likely to experience further weight loss when they remain on the drug for maintenance therapy up to 48 weeks, a new study shows.

Researchers gave 902 adults with overweight or obesity weekly injections of semaglutide. After 20 weeks, researchers randomized 803 participants who reached a maintenance dose of 2.4 mg/wk 1:1 to continue taking this dose weekly or to switch to placebo for 48 weeks. Both groups also received lifestyle intervention.

During the 20-week run-in, mean weight loss had been 10.6% of body weight. Participants who continued on semaglutide maintenance therapy had mean body weight loss of 7.9% from week 20 to week 68, compared with mean body weight gain of 6.9% among those who switched to placebo.

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"In my clinical experience, individuals who are able to achieve this level of weight loss, see and feel the impact on both comorbidities and their quality of life, and these improvements may also help sustain lifestyle changes," said lead study author Dr. Domenica Rubino, director of the Washington Center for Weight Management and Research, in Arlington, Virginia.

"Medical options are needed to target this complex physiologic regulation of weight that makes maintenance difficult," Dr. Rubino said by email. "Semaglutide 2.4 mg may be one of these options."

Compared to placebo, participants on semaglutide maintenance therapy also had significantly bigger improvements in waist circumference (-9.7cm), systolic blood pressure (-3.9 mmHG), and physical functioning scores assessed by the Short Form 36 Version 2 Health Survey Acute Version (SF-36) (2.5-points higher score).

The most common side effects were gastrointestinal events, which impacted 49.1% on semaglutide compared with 26.1% on placebo. However, there was no meaningful difference in the proportion of patients on semaglutide (2.4%) and placebo (2.2%) who discontinued treatment due to side effects.

During the initial 20 weeks of the trial, 2.3% of participants reported serious adverse events, as did 7.7% who continued on semaglutide and 5.6% who switched to placebo. There was one death in each group, and the fatalities were determined to be unrelated to the study treatment.

One limitation of the study is that maintenance therapy was only evaluated in patients who could tolerate the strict dose titration schedule at the start of the study, the authors note in JAMA. Participants in the study were likely more tolerant of therapy and more adherent to treatment than would occur in the community, they add.

However, the results underscore that medication for weight loss should be considered as an ongoing intervention, much like medication for other chronic diseases, said Dr. Robert Kushner, director of the Center for Lifestyle Medicine at Northwestern University Feinberg School of Medicine, in Chicago.

"We no longer consider use of medication for obesity as a jump start," Dr. Kushner, who wasn't involved in the study, said by email.

"Instead, we consider obesity as a chronic progressive and relapsing disease for many patients who suffer from excess weight," Dr. Kushner said. "Thus, similar to adapting a healthy lifestyle that will last a lifetime, many individuals would benefit from long-term treatment with medication."

—Lisa Rapaport

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