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Title: Efficacy and safety of methionine aminopeptidase 2 inhibition in type 2 diabetes: a randomised, placebo-controlled clinical trial.
Austin Authors: Proietto, Joseph ;Malloy, Jaret;Zhuang, Dongliang;Arya, Mark;Cohen, Neale D;de Looze, Ferdinandus J;Gilfillan, Christopher;Griffin, Paul;Hall, Stephen;Nathow, Thomas;Oldfield, Geoffrey S;O'Neal, David N;Roberts, Adam;Stuckey, Bronwyn G A;Yue, Dennis;Taylor, Kristin;Kim, Dennis
Affiliation: Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Discipline of General Practice, Faculty of Medicine, University of Queensland, Herston, QLD, Australia
AusTrials Pty Ltd, Sherwood, QLD, Australia
Australian Clinical Research Network, Maroubra, NSW, Australia
Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
Eastern Health Clinical School, Monash University, Box Hill, Victoria, Australia
Q-Pharm Pty Ltd, Herston, QLD, Australia
QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
Mater Health Services, South Brisbane, QLD, Australia
Faculty of Medicine, University of Queensland, Herston, QLD, Australia
Emeritus Research, Malvern East, Victoria, Australia
Institution for Rehabilitation Research, Monash University, Clayton, Victoria, Australia
Ipswich Research Institute, Ipswich, QLD, Australia
Pendlebury Research, Cardiff, NSW, Australia
Department of Medicine, University of Melbourne, St Vincent's Hospital, Fitzroy, Victoria, Australia
University Hospital Geelong, Geelong, Victoria, Australia
Keogh Institute for Medical Research, University of Western Australia, Nedlands, WA, Australia
Royal Prince Alfred Hospital, Camperdown, NSW, Australia
Zafgen, Inc., 175 Portland St, 4th Floor, Boston, MA, 02114, USA
Issue Date: 11-Jul-2018
Date: 2018-07-11
Publication information: Diabetologia 2018; 61(9): 1918-1922
Abstract: This multicentre randomised double-blind placebo-controlled clinical trial assessed the efficacy and safety of a methionine aminopeptidase 2 (MetAP2) inhibitor, beloranib, in individuals with obesity (BMI ≥30 kg/m2) and type 2 diabetes (HbA1c 53-97 mmol/mol [7-11%] and fasting glucose <15.6 mmol/l). Participants were randomised (via a centralised interactive web response system) to placebo, 1.2 or 1.8 mg beloranib s.c. twice weekly for 26 weeks. Participants, investigators and the sponsor were blinded to group assignment. The primary endpoint was the change in weight from baseline to week 26. The trial was terminated early when beloranib development was stopped because of an imbalance of venous thromboembolism events in beloranib-treated individuals vs placebo that became evident during late-stage development of the drug. In total, 153 participants were randomised, 51 to placebo, 52 to 1.2 mg beloranib and 50 to 1.8 mg beloranib. In participants who completed week 26, the least squares mean ± SE weight change (baseline 111 kg) was -3.1 ± 1.2% with placebo (n = 22) vs -13.5 ± 1.1% and -12.7 ± 1.3% with 1.2 and 1.8 mg beloranib, respectively (n = 25; n = 19; p < 0.0001). The change in HbA1c (baseline 67 mmol/mol [8.3%]) was -6.6 ± 2.2 mmol/mol (-0.6 ± 0.2%) with placebo vs -21.9 ± 2.2 mmol/mol (-2.0 ± 0.2%) or -21.9 ± 3.3 mmol/mol (-2.0 ± 0.3%) with 1.2 or 1.8 mg beloranib (p < 0.0001), respectively. The most common beloranib adverse events were sleep related. One beloranib-treated participant experienced a non-fatal pulmonary embolism. MetAP2 inhibitors represent a novel mechanism for producing meaningful weight loss and improvement in HbA1c. NCT02324491 FUNDING: The study was funded by Zafgen, Inc.
DOI: 10.1007/s00125-018-4677-0
Journal: Diabetologia
PubMed URL: 29992370
Type: Journal Article
Subjects: Anti-obesity medication
Glucose-lowering medication
Glycaemic control
Appears in Collections:Journal articles

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