Liraglutide and Weight Loss Among Suboptimal Responders to Metabolic Bariatric Surgery

Importance: Suboptimal weight loss after metabolic bariatric surgery (MBS) is a common indication for conversion surgery. The use of obesity management medications may improve weight loss, reducing the need for further surgery. Objective: To examine whether liraglutide improves weight loss and health outcomes after MBS in patients who have had suboptimal weight loss. Design, Setting, and Participants: This prospective, double-blinded, single-center randomized clinical trial compared the effect of daily liraglutide with placebo in adults treated at an academic surgical department. Patients with anatomically correct adjustable gastric band, sleeve gastrectomy, one anastomosis gastric bypass, or Roux-en-Y gastric bypass (confirmed with barium swallow and/or endoscopy) were invited to participate at 12 to 36 months after surgery if they had a body mass index greater than 35 (calculated as weight in kilograms divided by height in meters squared), were aged 20 to 65 years, and had achieved a stable weight (defined as a weight consistently within a 4-kg range during a 3-month period) with an excess body weight loss (defined using body mass index threshold of 25) of 25% to 40% or total body weight loss of 5% to 12% for anatomically correct adjustable gastric band and excess body weight loss of 25% to 60% or total body weight loss of 10% to 20% for sleeve gastrectomy, Roux-en-Y gastric bypass, and one anastomosis gastric bypass. The first participant was randomized on January 18, 2019, and the last on June 9, 2023. Primary data analysis occurred on July 15, 2024. Intervention: Study intervention was liraglutide or placebo self-administered daily by participants. Participants self-titrated dosing. Treatment was intended for 12 months. Main Outcomes and Measures: Primary outcome was weight loss at 12 months. Change in health and quality of life were secondary measures. Results: The study included 24 participants in each arm (liraglutide arm: mean [SD] age, 48.7 [10.5] years; 22 [92%] female; placebo arm: mean [SD] age, 43.6 [11.4] years; 20 [83%] female). In the liraglutide arm, 4 patients withdrew and 1 was lost to follow-up. In the placebo arm, 6 patients withdrew and 6 were lost to follow-up. At 12 months, mean (SE) weight loss in the liraglutide group was 5.7 (1.1) kg with a mean (SD) weight gain of 1.4 (1.2) kg in the placebo group (between-group difference, 7.1 kg [95% CI, 3.9-10.3 kg]; P < .001). There were no adverse effects on health or quality of life. Conclusions and Relevance: In this randomized clinical trial, liraglutide provided greater weight loss at 12 months than placebo in a cohort of patients with a suboptimal response to MBS. These results suggest that combining obesity management medications with MBS affords the opportunity to increase weight loss for those with a suboptimal initial response or weight regain, potentially avoiding conversion surgery. Trial Registration: anzctr.org.au Identifier: ACTRN12617001613392.