Safety and Efficacy of Liraglutide, 3.0 mg, Once Daily vs Placebo in Patients With Poor Weight Loss Following Metabolic Surgery

Abstract

ImportanceMetabolic surgery leads to weight loss and improved health, but these outcomes are highly variable. Poor weight loss is associated with lower circulating levels of glucagon-like peptide-1 (GLP-1).ObjectiveTo assess the efficacy and safety of the GLP-1 receptor agonist, liraglutide, 3.0 mg, on percentage body weight reduction in patients with poor weight loss and suboptimal GLP-1 response after metabolic surgery.Design, Setting, and ParticipantsThe Evaluation of Liraglutide 3.0 mg in Patients With Poor Weight Loss and a Suboptimal Glucagon-Like Peptide-1 Response (BARI-OPTIMISE) randomized placebo-controlled trial recruited adult patients at least 1 year after metabolic surgery who had experienced 20% or less body weight loss from the day of surgery and a suboptimal nutrient-stimulated GLP-1 response from 2 hospitals in London, United Kingdom, between October 2018 and November 2019. Key exclusion criteria were type 1 diabetes; severe concomitant psychiatric, gastrointestinal, cardiac, kidney or metabolic disease; and use of insulin, GLP-1 receptor analogues, and medication that can affect weight. The study period was 24 weeks followed by a 4-week follow-up period. Last participant follow-up was completed in June 2020. All participants and clinical study personnel were blinded to treatment allocation. Of 154 assessed for eligibility, 70 met trial criteria and were included in the study, and 57 completed follow-up.InterventionsLiraglutide, 3.0 mg, once daily or placebo as an adjunct to lifestyle intervention with a 500-kcal daily energy deficit for 24 weeks, on a 1:1 allocation by computer-generated randomization sequence, stratified by surgery type (Roux-en-Y gastric bypass [RYGB] or sleeve gastrectomy [SG]) and type 2 diabetes status.Main Outcome and MeasuresThe primary outcome was change in percentage body weight from baseline to the end of the 24-week study period based on an intention-to-treat analysis. Participant safety was assessed through monitoring of biochemical parameters, including kidney and liver function, physical examination, and assessment for adverse events.ResultsA total of 70 participants (mean [SD] age, 47.6 [10.7] years; 52 [74%] female) with a poor weight loss response following RYGB or SG were randomized to receive 3.0-mg liraglutide (n = 35) or placebo (n = 35). All participants received at least 1 dose of the trial drug. Eight participants discontinued treatment (4 per group), and 2 in the 3.0-mg liraglutide group and 1 in the placebo group were lost to follow-up. Due to COVID-19 restrictions, 3 participants in the 3.0-mg liraglutide group and 7 in the placebo group were unable to attend their final in-person assessment. Estimated change in mean (SD) percentage body weight from baseline to week 24 was −8.82 (4.94) with liraglutide, 3.0 mg (n = 31), vs −0.54 (3.32) with placebo (n = 26). The mean difference in percentage body weight change for liraglutide, 3.0 mg, vs placebo was −8.03 (95% CI, −10.39 to −5.66; P < .001). Adverse events, predominantly gastrointestinal, were more frequent with liraglutide, 3.0 mg (28 events [80%]), than placebo (20 events [57%]). There were no serious adverse events and no treatment-related deaths.Conclusion and RelevanceThese findings support the use of adjuvant liraglutide, 3.0 mg, for weight management in patients with poor weight loss and suboptimal GLP-1 response after metabolic surgery.Trial RegistrationClinicalTrials.gov Identifier: NCT03341429

Adverse Event Comparison between Glucagon-like Peptide-1 Receptor Agonists and Other Anti-Obesity Medications Following Bariatric Surgery

“…11,12 These findings align with prior studies which primarily reported mild to moderate GI side effects ranging in frequency from 30-50% with discontinuation rates of 5-9%. [13][14][15][16] GLP1RA AOMs do not appear to lead to a heightened risk of adverse events in patients who have previously undergone bariatric surgery.…”

“…18 Two randomized trials investigating Liraglutide in patients with prior bariatric surgery demonstrated efficacy with 8% additional weight loss (compared to placebo), and liraglutide was well tolerated in these trials with no SAE. 16,19 Two observational studies by Bonnett and Murvelashvili each reported that among patients with prior bariatric surgery, semaglutide can achieve 9 – 13% weight loss with a year of treatment. 20,21 In order to realize the potential of adjuvant AOM, rigorous studies are needed to develop practice guidelines that direct the use of AOMs as adjuvant therapy.…”

Special considerations for the adolescent with obesity: An obesity medicine association (OMA) clinical practice statement (CPS) 2024

“…This section focuses on adolescents who are post-MBS and when they may benefit from the addition of AOM's as an adjunct therapy. The available MBS data for children [ [20] , [21] , [22] , [23] , [24] , 66 ] and adults [ [67] , [68] , [69] , [70] , [71] , [72] ] is examined for the variety of responses to MBS ( Table 2 ). This information is provided as guidance for the pediatric obesity medicine team.…”

“… −6 months of semaglutide treatment: −85 % of patients achieved >5 % weight loss −45 % reached >10 % weight loss −5% achieved >15 % weight loss. -No weight loss difference based on type of MBS Patients started semaglutide on average 64.7 months after MBS Mok et al., 2023 [ 69 ] 70 participants -poor weight loss response following RYGB or SG -randomized to receive 3.0-mg liraglutide (n = 35) or placebo (n = 35). -Poor response defined as < 20 % TBWL more than 1 year after MBS.…”

Treatment of Severe Obesity—All-Hands-on-Deck Approach

“…The BARI-OPTIMISE trial reported a difference of 8% further total body weight loss at 6 months between 35 patients randomized to receive liraglutide, 3.0 mg, and 35 patients randomized to placebo. 3 Similarly, the Gauging Responsiveness With a VerifyNow Assay-Impact on Thrombosis and Safety (GRAVITAS) trial using liraglutide, 1.8 mg, for persistent or recurrent diabetes in 80 patients with MBS demonstrated superior weight loss in the short-term compared with placebo as a secondary outcome. 4 The additional weight loss with associated favorable metabolic changes achieved with liraglutide…”