Adjunctive liraglutide treatment in patients with persistent or recurrent type 2 diabetes after metabolic surgery (GRAVITAS): a randomised, double-blind, placebo-controlled trial

Abstract

Background: Obesity surgery is effective for obesity and type 2 diabetes (T2DM). However, many patients do not achieve sustained diabetes remission following surgery. Liraglutide, a GLP-1 analogue, improves glycaemia and reduces body weight. Our aim was to evaluate the safety and effectiveness of Liraglutide 1•8 mg in patients with persistent or recurrent T2DM after surgery. Methods: In this double-blind, placebo-controlled trial, adults with HbA1c >48 mmol/mol (>6•5%) at least one year after surgery were randomised 2:1 to once-daily subcutaneous Liraglutide 1•8 mg or Placebo, together with a reduced-calorie diet and increased physical activity. The primary outcome was the change in HbA1c from baseline to 26 weeks. EudraCT 2014-003923-23 and ISRCTN 13643081. Findings: Between February 2016 and November 2018, we assigned 80 patients to receive Liraglutide (n=53) or Placebo (n=27). Seventy-one (89%) participants completed the study up to week 26 (complete-cases population). A multivariable linear regression analysis taking baseline HbA1c and type of surgery into account as covariates showed that Liraglutide was associated with a difference in HbA1c change of-13•3 mmol/mol or-1•22%, 95% CI-19•7 to-7•0, p<0•001) vs Placebo at 26 weeks. Liraglutide was associated with a difference in the change of weight of-4•23 kg [95% CI-6•81 to-1•64, p<0•001) vs Placebo. No significant influence of type of surgery was noted. Interpretation: This is the first randomised controlled trial of adjunctive Liraglutide treatment in patients with diabetes mellitus after metabolic surgery. The results support the use of Liraglutide therapy in this clinical context. Funding: JP Moulton Charitable Foundation 3 surgery. We have previously shown that the acute peripheral administration of the GLP-1 RA Exendin-4 in rodent models of RYGB has additive effects to the already enhanced endogenous GLP-1 secretion as demonstrated by an additional reduction in food intake 11. Indeed, data from retrospective non-randomised studies in humans support this hypothesis: the administration of GLP-1 RAs in patients with and without T2DM and a suboptimal response to metabolic surgery was associated with weight loss and glycaemic improvements 12-15. This RCT was therefore designed to investigate the safety and efficacy of pharmacological administration of the GLP-1 RA Liraglutide on glycaemic control in patients with persistent or recurrent T2DM after RYGB or VSG surgery. Methods Study population This was a prospective randomised double-blinded placebo-controlled clinical trial. Eighty patients with obesity and persistent or recurrent T2DM that had undergone RYGB or VSG surgery at least 12 months before randomisation were recruited from the

Reversal of Long-Term Weight Regain After Roux-en-Y Gastric Bypass Using Liraglutide or Surgical Revision. A Prospective Study

“…Similarly, a study in RYGB or gastric banding patients [15] resulted in a median weight loss of 7 kg after 8 months. Moreover, in a short-term randomized clinical trial of 28 weeks, patients with obesity were successfully and safely treated with subcutaneous liraglutide (1.8 mg daily) for persistent or recurrent T2D [16] more than 1 year after bariatric surgery (RYGB or sleeve resection). Studies comparing medical, surgical (i.e., reoperation or endosurgery), or lifestyle interventions for managing insufficient weight loss or weight regain more than 6 years after RYGB surgery are scarce [17] and need further medical validation.…”

The Mitigating Effect of Phentermine and Topiramate on Weight Regain After Roux‐en‐Y Gastric Bypass Surgery

“…There are few prospective trials investigating “rescue” pharmacotherapy with AOMs following bariatric surgery, with only six published to date with small numbers of patients (37‐43). One of the studies used an AOM which has since been withdrawn from the market, fenfluramine (40), and two other trials used AOMs after the adjustable laparoscopic gastric band, which is rarely used today (41,42).…”

The effectiveness and safety of pharmaceuticals to manage excess weight post-bariatric surgery: a systematic literature review

“…Due to the dearth of research in this area, there is a need for more research with direct comparisons of post-bariatric surgery to non-post bariatric surgery patients, and to post-bariatric surgery patients prescribed a placebo to establish the efficacy of weight loss agents in post-bariatric surgery populations, which is already underway. For example, there is a randomized control trial by Miras et al (2019) 19 published after the dates of this review. The authors compared the use of liraglutide 1.8 mg in post-bariatric surgery patients.…”