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

Title: Adjunctive liraglutide treatment in patients with persistent or recurrent type 2 diabetes after metabolic surgery (GRAVITAS): a randomised, double-blind, placebo-controlled trial
Authors: Miras, AD
Pérez-Pevida, B
Aldhwayan, M
Kamocka, A
McGlone, ER
Al-Najim, W
Chahal, H
Batterham, RL
McGowan, B
Khan, O
Greener, V
Ahmed, AR
Petrie, A
Scholtz, S
Bloom, SR
Tan, TM
Item Type: Journal Article
Abstract: Background Many patients with type 2 diabetes do not achieve sustained diabetes remission after metabolic (bariatric) surgery for the treatment of obesity. Liraglutide, a glucagon-like peptide-1 analogue, improves glycaemic control and reduces bodyweight in patients with type 2 diabetes. Our aim was to assess the safety and efficacy of liraglutide 1·8 mg in patients with persistent or recurrent type 2 diabetes after metabolic surgery. Methods In the GRAVITAS randomised double-blind, placebo-controlled trial, we enrolled adults who had undergone Roux-en-Y gastric bypass or vertical sleeve gastrectomy and had persistent or recurrent type 2 diabetes with HbA1c levels higher than 48 mmol/mol (6·5%) at least 1 year after surgery from five hospitals in London, UK. Participants were randomly assigned (2:1) via a computer-generated sequence to either subcutaneous liraglutide 1·8 mg once daily or placebo, both given together with a reduced-calorie diet, aiming for a 500 kcal per day deficit from baseline energy intake, and increased physical activity. The primary outcome was the change in HbA1c from baseline to the end of the study period at 26 weeks, assessed in patients who completed the trial. Safety was assessed in the safety analysis population, consisting of all participants who received either liraglutide or placebo. This trial is registered with EudraCT, number 2014-003923-23, and the ISRCTN registry, number ISRCTN13643081. Findings Between Jan 29, 2016, and May 2, 2018, we assigned 80 patients to receive either liraglutide (n=53) or placebo (n=27). 71 (89%) participants completed the study and were included in the principal complete-cases analysis. In a multivariable linear regression analysis, with baseline HbA1c levels and surgery type as covariates, liraglutide treatment was associated with a difference of −13·3 mmol/mol (−1·22%, 95% CI −19·7 to −7·0; p=0·0001) in HbA1c change from baseline to 26 weeks, compared with placebo. Type of surgery had no significant effect on the outcome. 24 (45%) of 53 patients assigned to liraglutide and 11 (41%) of 27 assigned to placebo reported adverse effects: these were mainly gastrointestinal and in line with previous experience with liraglutide. There was one death during the study in a patient assigned to the placebo group, which was considered unrelated to study treatment. Interpretation These findings support the use of adjunctive liraglutide treatment in patients with persistent or recurrent type 2 diabetes after metabolic surgery. Funding JP Moulton Foundation.
Issue Date: Jul-2019
Date of Acceptance: 22-Apr-2019
URI: http://hdl.handle.net/10044/1/85812
DOI: 10.1016/s2213-8587(19)30157-3
ISSN: 2213-8587
Publisher: Elsevier BV
Start Page: 549
End Page: 559
Journal / Book Title: The Lancet Diabetes & Endocrinology
Volume: 7
Issue: 7
Copyright Statement: © 2019 Elsevier Ltd. All rights reserved. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/
Sponsor/Funder: J P Moulton Charitable Foundation
Royal College of Surgeons of England
Medical Research Council (MRC)
The Jon Moulton Charity Trust
The Jon Moulton Charity Trust
Fractyl Laboratories, Inc.
Imperial College Healthcare NHS Trust
Imperial College Healthcare NHS Trust
Funder's Grant Number: SR Bloom GRAVITAS 2014
RCS 1 year fellowship
G0902002
Prof Alex Miras
WREE_P84939
4581
FR420
FR717
Keywords: Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
Y GASTRIC BYPASS
DUTCH EATING BEHAVIOR
BARIATRIC SURGERY
WEIGHT-LOSS
SLEEVE GASTRECTOMY
GUT HORMONES
FOOD-INTAKE
REMISSION
QUESTIONNAIRE
EXPENDITURE
Aged
Bariatric Surgery
Diabetes Mellitus, Type 2
Double-Blind Method
Female
Humans
Hypoglycemic Agents
Liraglutide
Male
Middle Aged
Postoperative Complications
Humans
Diabetes Mellitus, Type 2
Postoperative Complications
Hypoglycemic Agents
Double-Blind Method
Aged
Middle Aged
Female
Male
Bariatric Surgery
Liraglutide
1101 Medical Biochemistry and Metabolomics
1103 Clinical Sciences
1117 Public Health and Health Services
Publication Status: Published
Open Access location: https://discovery.ucl.ac.uk/id/eprint/10083662/
Online Publication Date: 2019-06-04
Appears in Collections:Department of Medicine (up to 2019)



This item is licensed under a Creative Commons License Creative Commons