Liraglutide promotes weight loss after suboptimal response to bariatric surgery

For patients who are struggling to lose weight after metabolic bariatric surgery (MBS), treatment with liraglutide boosts weight-loss outcomes and helps avoid conversion surgery, as shown in a randomized clinical trial.

Over 12 months of treatment, liraglutide-treated patients experienced a mean weight loss of 5.7 kg, whereas those who received placebo saw a mean weight gain of 1.4 kg (between-group difference, 7.1 kg, 95 percent confidence interval [CI], 3.9–10.3; p<0.001). In terms of percentage, weight decreased by a mean of 4.4 percent with liraglutide and increased by a mean of 1.4 percent with placebo (p<0.001). [JAMA Netw Open 2025;8:e2539848]

“There is great heterogeneity in weight response to all obesity therapies, including MBS. Our demonstration of safety and efficacy of [liraglutide among individuals who had undergone MBS] suggests that obesity management medications might be used earlier after MBS rather than waiting for suboptimal weight loss or weight regain,” the investigators said. [Lancet 2023;401:1116-1130]

They emphasized that the addition of obesity management medications could help avoid or delay the need for conversion surgery, which carries an increased risk of mortality and morbidity. Furthermore, the amount of weight loss after the conversion procedure is typically less than the weight loss achieved from a primary procedure of the same type. [Obes Surg 2024;34:1764-1777; Int J Surg 2022;102:106677; Surg Obes Relat Dis 2023;19:111-117]

Study details

For the study, the investigators recruited adults with anatomically correct adjustable gastric band, sleeve gastrectomy, one anastomosis gastric bypass, or Roux-en-Y gastric bypass. The inclusion criteria were a BMI of >35 kg/m², stable weight (within a 4-kg range during a 3-month period), and excess body weight loss of 25–40 percent or total body weight loss of 5–12 percent for anatomically correct adjustable gastric band or excess body weight loss of 25–60 percent or total body weight loss of 10–20 percent for sleeve gastrectomy, Roux-en-Y gastric bypass, and one anastomosis gastric bypass. A total of 48 patients were included.

At 12–36 months after MBS, the patients were randomly assigned to receive liraglutide (n=24; mean age 48.7 years, 92 percent female) or placebo (n=24; mean age 43.6 years, 83 percent female) in prefilled multidose disposable pens and self-administered daily. Participants were instructed to start at a dose of 0.6 mg at week 1, gradually increasing by 0.6 mg/d per week until 3 mg was reached by week 5. Treatment was intended for 12 months.

The mean overall dose of self-administered medication was 2.43 mg in the liraglutide group vs 2.20 mg in the placebo group (p=0.003). None of the participants experienced grade ≥3 adverse events during the trial.

Liraglutide was associated with an increase in diastolic BP, from a mean of 78 mm Hg at baseline to 82 mm Hg at 12 months (p=0.02); diastolic BP remained unchanged with placebo. Additionally, mean SF-36 pain scores were lower with liraglutide vs placebo (70.4 vs 86.3; p=0.04), whereas mean physical functioning scores were higher with placebo vs liraglutide (92.5 vs 76.1; p=0.04).

“Although the SF-36 physical functioning scores were lower at 12 months in the group treated with liraglutide, there was no significant difference to placebo when comparing the change from commencement of the trial,” the investigators noted.

“There was no deleterious effect of liraglutide on quality of eating and swallowing, which is important given that GLP analogues delay gastric emptying and increase reflux,” they added. [Obes Sci Pract 2017;3:3-14]

Of note, liraglutide-treated participants took less than the standard maximum dose of 3 mg/d at all time points, according to the investigators. “It is possible that patients were happy with the weight-loss effect at lower doses or that adverse effects limited further escalation.”

They called for further investigation to confirm whether the full dose of obesity management medications is required in conjunction with MBS.