Alexander Dimitri Miras1, Belén Pérez-Pevida1, Madhawi Aldhwayan1, Anna Kamocka1, Emma Rose McGlone1, Werd Al-Najim2, Harvinder Chahal1, Rachel L Batterham3, Barbara McGowan4, Omar Khan5, Veronica Greener6, Ahmed R Ahmed7, Aviva Petrie8, Samantha Scholtz1, Stephen R Bloom1, Tricia M Tan9. 1. Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London and Imperial College Healthcare NHS Trust, London, UK. 2. Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London and Imperial College Healthcare NHS Trust, London, UK; Diabetes Complications Research Centre, Conway Institute, University College Dublin, Dublin, Ireland. 3. Centre for Obesity Research, Rayne Institute, Department of Medicine, University College London, London, UK; Bariatric Centre for Weight Management and Metabolic Surgery and National Institute for Health Research Biomedical Research Centre, University College London Hospital, London, UK. 4. Diabetes and Endocrinology, Guy's and St Thomas' NHS Foundation Trust, London, UK. 5. Surgery, St George's University Hospitals NHS Trust, London, UK. 6. Diabetes and Endocrinology, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK. 7. Department of Surgery & Cancer, Imperial College London and Imperial College Healthcare NHS Trust, London, UK. 8. Eastman Dental Institute, University College London, London, UK. 9. Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London and Imperial College Healthcare NHS Trust, London, UK. Electronic address: t.tan@imperial.ac.uk.
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.
RCT Entities:
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.
Authors: Nawfal W Istfan; Wendy A Anderson; Donald T Hess; Liqun Yu; Brian Carmine; Caroline M Apovian Journal: Obesity (Silver Spring) Date: 2020-06 Impact factor: 5.002
Authors: Nawfal W Istfan; Marine Lipartia; Wendy A Anderson; Donald T Hess; Caroline M Apovian Journal: J Clin Endocrinol Metab Date: 2021-01-01 Impact factor: 5.958
Authors: Sandeep R Das; Brendan M Everett; Kim K Birtcher; Jenifer M Brown; James L Januzzi; Rita R Kalyani; Mikhail Kosiborod; Melissa Magwire; Pamela B Morris; Joshua J Neumiller; Laurence S Sperling Journal: J Am Coll Cardiol Date: 2020-08-05 Impact factor: 24.094