The methionine aminopeptidase 2 inhibitor ZGN-1061 improves glucose control and weight in overweight and obese individuals with type 2 diabetes: a randomized placebo-controlled trial
- Author(s)
- Wentworth, JM; Colman, PG; Zafgen Study Group,;
- Journal Title
- Diabetes Obesity & Metabolism
- Publication Type
- Journal epub ahead of print
- Abstract
- The methionine aminopeptidase 2 (MetAP2) inhibitor ZGN-1061 lowered weight and improved glucose in preclinical studies. We sought to determine its efficacy and safety by performing a multi-center Phase 2 randomized controlled trial involving overweight and obese adults with type 2 diabetes and HbA1c between 7 and 11% inclusive. Participants were randomized to receive subcutaneous treatment with placebo or 0.05mg, 0.3mg, 0.9mg or 1.8mg ZGN-1061 every 3rd day for 12 weeks. The primary outcome was DeltaHbA1c at week 12. Relative to placebo, the 0.9mg and 1.8mg doses induced clinically meaningful reductions in HbA1c of 0.6% (95% CI 0.2 to 0.9; p=0.0006) and 1.0% (95% CI 0.6 to 1.4; p<0.0001) respectively. The 1.8mg dose also induced weight loss of 2.2% (95% CI 1.1 to 3.3; p=0.0002). The incidence of adverse events was balanced across the treatment groups. We conclude that MetAP2 inhibition with ZGN-1061 for 12 weeks improved glucose control and aided weight loss in overweight and obese people with type 2 diabetes. However, given safety issues, Zafgen has discontinued MetAP2 inhibitor development. This article is protected by copyright. All rights reserved.
- Publisher
- Wiley
- Research Division(s)
- Population Health And Immunity
- PubMed ID
- 32077231
- Publisher's Version
- https://doi.org/10.1111/dom.14009
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2020-03-20 11:26:19
Last Modified: 2020-03-26 02:23:47