Liraglutide Could Improve Weight Loss after Poor Response to Metabolic Surgery

Rachel L. Batterham, MBBS, PhD

Credit: Obesity Update

New research supports the role of liraglutide, 3.0 mg, for weight management in individuals with poor weight loss and suboptimal glucagon-like peptide-1 (GLP-1) response after metabolic surgery.¹

Results from the BARI-OPTIMISE randomized clinical trial suggest 24 weeks of 3.0 mg liraglutide as an adjunct to lifestyle intervention was both safe and well-tolerated, leading to clinically meaningful reductions in body weight for these patients compared with placebo.

“Our findings show that liraglutide, 3.0 mg, for 24 weeks led to a significantly greater reduction in percentage body weight compared to placebo, coupled with reduced fat mass, favorable changes in cardiometabolic risk factors, and improvement in health-related quality of life,” wrote the investigative team, led by Rachel L. Batterham, MBBS, PhD, division of medicine, University College London Centre for Obesity Research, Rayne Institute.

Metabolic surgery remains the most effective known treatment option for people with severe obesity, but responses can be highly variable, particularly on an individual level. Approximately 1 in 4 patients who undergo metabolic surgery experience poor weight loss or weight regain, resulting in ≤20% weight loss.² Evidence has shown individuals with poor weight loss may have increased appetite and lower circulating levels of GLP-1 and therefore may see benefit with GLP-1 analog treatment.

The double-blinded, randomized, placebo-controlled, parallel-group trial BARI-OPTIMISE trial aimed to confirm the superiority of 3.0 mg liraglutide, compared to placebo on percentage body weight reduction, as an adjunct to lifestyle intervention (500 kcal deficit), in patients with poor weight loss and suboptimal GLP-1 response ≥1 year after metabolic surgery. A suboptimal response was defined as a ≤2-fold increase in circulating active GLP-1 between 0 - 30 minutes following a meal.

Patients were screened between September 2018 - October 2019 and treated between October 2018 - November 2019 at 2 hospitals in London, United Kingdom. Included participants were randomly assigned in a 1:1 ratio to either liraglutide, 3.0 mg, or placebo and stratified by surgery type (Roux-en-Y gastric bypass or sleeve gastrectomy) and type 2 diabetes status.

For the purpose of analysis, the primary outcome was the change in percentage body weight from baseline to the end of the 24-week study period, based on an intention-to-treat analysis. The safety of participants was assessed through monitoring of biochemical parameters, including kidney and liver function, physical examination, and assessment for adverse events.

Of 154 patients assessed for eligibility, 70 participants, with a mean age of 47.6 years, were randomized to 3.0 mg liraglutide once daily (n = 35) or placebo plus lifestyle intervention (n = 35). All participants who completed the trial escalated to 3.0 mg liraglutide once daily. After discontinuations, loss to follow-up, and lockdown restrictions due to the emergence of the COVID-19 pandemic, 31 participants in the 3.0 liraglutide group and 26 in the placebo group were included in the primary intention-to-treat analysis.

From baseline to week 24, the analysis revealed a greater reduction in percentage body weight in the 3.0 mg liraglutide group compared with placebo (mean, –8.82 vs. –0.54, respectively; P <.001). As a result, the mean difference in percentage body weight change was –8.03 (95% CI, –10.39 to –5.66; P <.001).

At the end of the treatment period, data showed 71.9% of participants treated with 3.0 mg liraglutide, compared with 8.8% in the placebo group, lost ≥5% of their baseline body weight. Safety outcomes reported adverse events, mostly gastrointestinal, were more frequent with 3.0 mg liraglutide (28 events [80%]) than with placebo (20 events [57%]), but there were no serious adverse events or treatment-related deaths.

Results from this trial reflect greater weight loss compared to corresponding trials of 3.0 mg liraglutide in people with overweight who have not undergone metabolic surgery, according to the investigative team.

“Importantly, participants in our trial did not reach weight loss nadir at the end of the 24-week treatment period, suggesting further weight reduction and health benefits may be achievable with a longer treatment period,” investigators wrote.

References

1. Mok J, Adeleke MO, Brown A, et al. Safety and Efficacy of Liraglutide, 3.0 mg, Once Daily vs Placebo in Patients With Poor Weight Loss Following Metabolic Surgery: The BARI-OPTIMISE Randomized Clinical Trial. JAMA Surg. Published online July 26, 2023. doi:10.1001/jamasurg.2023.2930
2. Brissman M, Beamish AJ, Olbers T, Marcus C. Prevalence of insufficient weight loss 5 years after Roux-en-Y gastric bypass: metabolic consequences and prediction estimates: a prospective registry study. BMJ Open. 2021;11(3):e046407. doi:10.1136/bmjopen-2020-046407