乌鸦传媒

Taking the GLP-1 receptor agonist liraglutide (Saxenda) might help bariatric surgery patients maintain weight loss, a double-blind, placebo-controlled study suggested.

In patients who had successfully lost at least 25% of their total body weight following bariatric surgery, but then regained at least 10%, once-daily liraglutide resulted in a median 9.65% drop in body weight from baseline to week 56, reported Holly Lofton, MD, of NYU Grossman School of Medicine in New York City.

Those randomized to placebo continued to regain weight -- regaining a median of 1.81% of baseline body weight (P<0.00001).

"These patients had already had some success [with surgery-induced weight loss] but then regained," Lofton said during a presentation of the findings at the ObesityWeek meeting. "We know that this particular surgery has been practiced since the 60s -- and even before -- and perfected by the many able surgeons who are practicing this every day for our patients, but we still are prone as humans to the outraces of metabolic adaptation. That our bodies really do want to regain weight, even as much as we alter with surgeries and medication, because that's a physiologic desire to survive a famine."

She pointed out that all patients in the study underwent lifestyle counseling, and that the near 2% weight regain seen with placebo occurred even with this intervention.

"The idea behind giving back this physiologic hormone in the GLP-1 speaks to the fact that we do need to think of surgery as a stage in the weight-loss treatment for someone, but it's not necessarily the final stage," she added. "Perhaps liraglutide can be one of the pharmacotherapeutic treatments that can help take patients to that next stage -- some even surpassing their post-surgical nadir with using this treatment."

Once-daily injectable liraglutide was FDA approved for chronic weight management at a 3 mg/day dose in conjunction with lifestyle management in adults with a body mass index (BMI) of 30 or higher, or with a BMI of ≥27 and at least one weight-related medical condition. This GLP-1 receptor agonist is also approved for type 2 diabetes at 1.2 mg/day and 1.8 mg/day doses under the trade name Victoza.

Novo Nordisk also recently had another GLP-1 receptor agonist approved for weight loss when paired with lifestyle management -- once-weekly injectable 2.4-mg semaglutide (Wegovy).

While less than 5% of patients on placebo in this study were able to lose 5% or more of baseline body weight during the follow-up period, the majority of those on liraglutide -- 69% -- were able to achieve this goal.

Additionally, 48% of patients on liraglutide were able to achieve a 10% or greater baseline body weight loss compared with no patients on placebo (P<0.0001), and 24% achieved a 15% or greater baseline body weight loss versus 0%, respectively (P<0.013).

Around a quarter of those on liraglutide were able to achieve -- or even surpass -- their postoperative nadir weight compared with none on placebo (P=0.024).

As for cardiometabolic profiles, those on liraglutide saw a drop in triglyceride levels over the 12-month follow-up. Although they didn't see much change in LDL, HDL, or total cholesterol levels, those on placebo saw a spike in LDL and total cholesterol and triglycerides, as well as a drop in HDL cholesterol.

The 132 patients included in the study had all undergone Roux-en-Y gastric bypass surgery and were 18 to 120 months postoperative (average 68 months). All patients had initially lost 25% or more of total body weight after surgery, but regained at least 10% or more after reaching their nadir weight. All also met the criteria for weight management pharmacotherapy.

The mean age in the total cohort was 47, and as expected with a bariatric surgery cohort, the vast majority were women (87%). More than half were white, and more than a quarter in each study arm were Black.

Patients were randomized in a 2:1 fashion, with 89 assigned to receive 3.0 mg/day of liraglutide compared with 43 patients on placebo. All participants attended clinic visits every 3 months, spanning from baseline to 56 weeks. Participants in both study arms received lifestyle counseling from registered dietitians.

Liraglutide was generally safe and well tolerated. The majority of the reported adverse events were expectedly gastrointestinal-related, including nausea, constipation, and abdominal pain. Of patients in the liraglutide arm, 4.5% experienced a serious adverse event versus 14% of the placebo arm. No deaths occurred in either group during the study.

Comment