Title |
Efficacy and safety of methionine aminopeptidase 2 inhibition in type 2 diabetes: a randomised, placebo-controlled clinical trial
|
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Published in |
Diabetologia, July 2018
|
DOI | 10.1007/s00125-018-4677-0 |
Pubmed ID | |
Authors |
Joseph Proietto, Jaret Malloy, Dongliang Zhuang, Mark Arya, Neale D. Cohen, Ferdinandus J. de Looze, Christopher Gilfillan, Paul Griffin, Stephen Hall, Thomas Nathow, Geoffrey S. Oldfield, David N. O’Neal, Adam Roberts, Bronwyn G. A. Stuckey, Dennis Yue, Kristin Taylor, Dennis Kim |
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. ClinicalTrials.gov NCT02324491 FUNDING: The study was funded by Zafgen, Inc. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Australia | 1 | 13% |
Germany | 1 | 13% |
Canada | 1 | 13% |
Unknown | 5 | 63% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 6 | 75% |
Scientists | 2 | 25% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 66 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 8 | 12% |
Student > Master | 7 | 11% |
Student > Doctoral Student | 6 | 9% |
Student > Bachelor | 5 | 8% |
Researcher | 5 | 8% |
Other | 10 | 15% |
Unknown | 25 | 38% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 16 | 24% |
Nursing and Health Professions | 5 | 8% |
Biochemistry, Genetics and Molecular Biology | 5 | 8% |
Sports and Recreations | 4 | 6% |
Agricultural and Biological Sciences | 1 | 2% |
Other | 9 | 14% |
Unknown | 26 | 39% |